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1.
J Diabetes Res ; 2020: 8205261, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33134395

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Asunto(s)
Infecciones por Coronavirus/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Enfermedades Endémicas , Malaria/epidemiología , Neumonía Viral/epidemiología , África/epidemiología , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Betacoronavirus/fisiología , Infecciones por Coronavirus/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Progresión de la Enfermedad , Humanos , Resistencia a la Insulina/fisiología , Malaria/complicaciones , Pandemias , Peptidil-Dipeptidasa A/fisiología , Neumonía Viral/complicaciones , Estado Prediabético/epidemiología , Estado Prediabético/patología , Estado Prediabético/virología , Sistema Renina-Angiotensina/efectos de los fármacos , Sistema Renina-Angiotensina/fisiología
2.
BMC Endocr Disord ; 20(1): 155, 2020 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-33066762

RESUMEN

BACKGROUND: Detailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2. CASE PRESENTATION: A 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement "resolved" at day 9, and the insulin infusion rate was rapidly reduced. CONCLUSIONS: This case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2. To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.


Asunto(s)
Betacoronavirus/aislamiento & purificación , Infecciones por Coronavirus/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Neumonía Viral/complicaciones , Infecciones por Coronavirus/transmisión , Infecciones por Coronavirus/virología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Diabetes Mellitus Tipo 2/virología , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/transmisión , Neumonía Viral/virología , Pronóstico
3.
Endokrynol Pol ; 71(5): 367-375, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33125688

RESUMEN

INTRODUCTION: The objective of this paper was to investigate the clinical features and pulmonary CT imaging features of COVID-19 patients with diabetes mellitus. MATERIAL AND METHODS: From January 16, 2020 to March 28, 2020, among the 568 cases of COVID-19 patients diagnosed in Xiaogan Central Hospital, 64 cases of COVID-19 patients with diabetes were selected as the diabetic group, and 64 cases of COVID-19 patients with age and gender matching without diabetes were selected as the non-diabetic group, and their clinical data and pulmonary CT characteristics were retrospectively analysed. RESULTS: Compared with the non-diabetic group, the proportion of patients in the diabetic group with chronic underlying disease was higher, and they were in more a serious condition at admission. Inflammation index and characteristics of glycolipid metabolism results showed that COVID-19 patients with diabetes mellitus were more likely to have elevated inflammatory markers and hypercoagulability, accompanied by hypoproteinaemia and glucose and lipid metabolism disorders. Treatment and clinic outcome results showed that the time of nucleic acid turning negative in the diabetic group was significantly longer than that in the non-diabetic group. Radiological data showed that COVID-19 combined with diabetes prolonged the time of detoxification in patients. CONCLUSION: COVID-19 patients with diabetes mellitus and chronic hypertension are associated with increased inflammatory markers and disorders of glucose and lipid metabolism. These patients tend to develop serious diseases, especially the rapid progression of CT lesions in the lungs of patients with a wide range ofinvolvement, and prolonged absorption and detoxification time.


Asunto(s)
Betacoronavirus , Infecciones por Coronavirus/diagnóstico por imagen , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Neumonía Viral/diagnóstico por imagen , Adulto , Anciano , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/complicaciones , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Neumonía Viral/complicaciones , Neumonía Viral/patología , Estudios Retrospectivos , Factores de Riesgo , Tomografía Computarizada por Rayos X
4.
Lancet Diabetes Endocrinol ; 8(10): 834-844, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32946820

RESUMEN

BACKGROUND: Although metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women. We aimed to investigate the effects of the addition of metformin to a standard regimen of insulin on neonatal morbidity and mortality in pregnant women with type 2 diabetes. METHODS: In this prospective, multicentre, international, randomised, parallel, double-masked, placebo-controlled trial, women with type 2 diabetes during pregnancy were randomly assigned from 25 centres in Canada and four in Australia to receive either metformin 1000 mg twice daily or placebo, added to insulin. Randomisation was done via a web-based computerised randomisation service and stratified by centre and pre-pregnancy BMI (<30 kg/m2 or ≥30 kg/m2) in a ratio of 1:1 using random block sizes of 4 and 6. Women were eligible if they had type 2 diabetes, were on insulin, had a singleton viable pregnancy, and were between 6 and 22 weeks plus 6 days' gestation. Participants were asked to check their fasting blood glucose level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Insulin doses were adjusted aiming for identical glucose targets (fasting glucose <5·3 mmol/L [95 mg/dL], 2-h postprandial glucose <6·7 mmol/L [120 mg/dL]). Study visits were done monthly and patients were seen every 1-4 weeks as was needed for standard clinical care. At study visits blood pressure and bodyweight were measured; patients were asked about tolerance to their pills, any hospitalisations, insulin doses, and severe hypoglycaemia events; and glucometer readings were downloaded to the central coordinating centre. Participants, caregivers, and outcome assessors were masked to the intervention. The primary outcome was a composite of fetal and neonatal outcomes, for which we calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes. The trial was registered with ClinicalTrials.gov, NCT01353391. FINDINGS: Between May 25, 2011, and Oct 11, 2018, we randomly assigned 502 women, 253 (50%) to metformin and 249 (50%) to placebo. Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome. We found no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; p=0·86; relative risk [RR] 1·02 [0·83 to 1·26]). Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA1c at 34 weeks' gestation 41·0 mmol/mol [SD 8·5] vs 43·2 mmol/mol [-10]; 5·90% vs 6·10%; p=0·015; mean glucose 6·05 [0·93] vs 6·27 [0·90]; difference -0·2 [-0·4 to 0·0]), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference -0·4 [95% CI -0·5 to -0·2]; p<0·0001), gained less weight (7·2 kg vs 9·0 kg; difference -1·8 [-2·7 to -0·9]; p<0·0001) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs 148 [63%] of 236 in the placebo group; relative risk [RR] 0·85 [95% CI 0·73 to 0·99]; p=0·031). We found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; p=0·93; RR 0·99 [0·72 to 1·35]). Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g [SD 742] vs 3375 g [742]; difference -218 [-353 to -82]; p=0·002), fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58 [0·34 to 0·97]; p=0·041), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65 [0·43 to 0·99]; p=0·046), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm [SD 5·0] vs 17·4 [6·2] mm; difference -1·41 [-2·6 to -0·2]; p=0·024; mean neonatal fat mass 13·2 [SD 6·2] vs 14·6 [5·0]; p=0·017). 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96 [1·10 to 3·64]; p=0·026). We found no significant difference in the cord c-peptide between groups (673 pmol/L [435] in the metformin group vs 758 pmol/L [595] in the placebo group; p=0·10; ratio of means 0·88 [0·72 to 1·02]). The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group). INTERPRETATION: We found several maternal glycaemic and neonatal adiposity benefits in the metformin group. Along with reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity and infant size measurements resulted in fewer large infants but a higher proportion of small-for-gestational-age infants. Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy. FUNDING: Canadian Institutes of Health Research, Lunenfeld-Tanenbaum Research Institute, University of Toronto.


Asunto(s)
Biomarcadores/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Adolescente , Adulto , Glucemia/análisis , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Hemoglobina A Glucada/análisis , Humanos , Agencias Internacionales , Persona de Mediana Edad , Embarazo , Resultado del Embarazo , Estudios Prospectivos , Adulto Joven
5.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-32895383

RESUMEN

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Asunto(s)
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Factor 1 de Crecimiento de Fibroblastos/administración & dosificación , Hipoglucemiantes/administración & dosificación , Hipotálamo/efectos de los fármacos , Proteínas Recombinantes/administración & dosificación , Proteína Relacionada con Agouti/metabolismo , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Glucemia/análisis , Comunicación Celular , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/etiología , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/etiología , Diabetes Mellitus Tipo 2/patología , Dieta Alta en Grasa/efectos adversos , Sacarosa en la Dieta/administración & dosificación , Sacarosa en la Dieta/efectos adversos , Humanos , Hipotálamo/citología , Hipotálamo/patología , Inyecciones Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormonas Estimuladoras de los Melanocitos/administración & dosificación , Ratones , Ratones Noqueados , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Oligodendroglía/efectos de los fármacos , Oligodendroglía/metabolismo , RNA-Seq , Receptor de Melanocortina Tipo 4/genética , Receptores de Melanocortina/antagonistas & inhibidores , Receptores de Melanocortina/metabolismo , Inducción de Remisión/métodos , Transducción de Señal/efectos de los fármacos , Análisis de la Célula Individual , Técnicas Estereotáxicas , Transcriptoma/efectos de los fármacos
6.
Front Immunol ; 11: 1582, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32793223

RESUMEN

Metabolic abnormalities such as dyslipidemia, hyperinsulinemia, or insulin resistance and obesity play key roles in the induction and progression of type 2 diabetes mellitus (T2DM). The field of immunometabolism implies a bidirectional link between the immune system and metabolism, in which inflammation plays an essential role in the promotion of metabolic abnormalities (e.g., obesity and T2DM), and metabolic factors, in turn, regulate immune cell functions. Obesity as the main inducer of a systemic low-level inflammation is a main susceptibility factor for T2DM. Obesity-related immune cell infiltration, inflammation, and increased oxidative stress promote metabolic impairments in the insulin-sensitive tissues and finally, insulin resistance, organ failure, and premature aging occur. Hyperglycemia and the subsequent inflammation are the main causes of micro- and macroangiopathies in the circulatory system. They also promote the gut microbiota dysbiosis, increased intestinal permeability, and fatty liver disease. The impaired immune system together with metabolic imbalance also increases the susceptibility of patients to several pathogenic agents such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, the need for a proper immunization protocol among such patients is granted. The focus of the current review is to explore metabolic and immunological abnormalities affecting several organs of T2DM patients and explain the mechanisms, whereby diabetic patients become more susceptible to infectious diseases.


Asunto(s)
Diabetes Mellitus Tipo 2/inmunología , Diabetes Mellitus Tipo 2/patología , Hiperglucemia/inmunología , Síndrome Metabólico/inmunología , Obesidad/inmunología , Betacoronavirus/inmunología , Infecciones por Coronavirus/inmunología , Susceptibilidad a Enfermedades/inmunología , Disbiosis/inmunología , Microbioma Gastrointestinal , Humanos , Sistema Inmunológico/metabolismo , Inflamación/inmunología , Estrés Oxidativo/inmunología , Pandemias , Neumonía Viral/inmunología
7.
Gene ; 763: 145058, 2020 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-32798635

RESUMEN

BACKGROUND: The nuclear receptors Rev-erb alpha and Rev-erb beta are transcription factors that regulate the function of genes in glucose and lipid metabolism, and they also form a link between circadian rhythm and metabolism. We evaluated the variations in Rev-erb alpha and Rev-erb beta genes together with biochemical parameters as risk factors in type 2 diabetic (T2DM) patients. METHODS: Molecular analyses of Rev-erb alpha and Rev-erb beta genes were performed on genomic DNA by using next-generation sequencing in 42 T2DM patients (21 obese and 21 non-obese) and 66 healthy controls. RESULTS: We found 26 rare mutations in the study groups, including 13 missense mutations, 9 silent mutations, 3 5'UTR variations, and a 3'UTR variation, of which 9 were novel variations (5 missense and 3 silent and 1 5'UTR). Six common variations were also found in the Rev-erb genes; Rev-erb beta Chr3:24003765 A > G, Rev-erb beta rs924403442 (Chr3:24006717) G > T, Rev-erb alpha Chr17:38253751 T > C, Rev-erb alpha rs72836608 C > A, Rev-erb alpha rs2314339 C > T and Rev-erb alpha rs2102928 C > T. Of these, Rev-erb beta Chr3:24003765 A > G was a novel missense mutation (p.Q197R), while others were identified as intronic variants. T2DM patients with Rev-erb beta rs924403442 T allele had lower body surface area (BSA) than noncarriers (GG genotype) (p = 0.039). Rev-erb alpha rs72836608 A allele and Rev-erb alpha rs2314339 CC genotype were associated with decreased serum HDL-cholesterol levels in T2DM patients (p = 0.025 and p = 0.027, respectively). In our study, different effects of Rev-erbs polymorphisms were found according to gender and presence of obesity. Rev-erb alpha rs72836608 (C > A) and rs2314339 (C > T) and Rev-erb alpha rs2102928 (C > T) were associated with low HDL-C levels in male T2DM patients. In female patients, Rev-erb alpha rs2102928 (C > T) was associated with high microalbuminuria and Rev-erb beta rs9244403442 G > T was associated with low HDL and high BSA values. In addition, Rev-erb alpha Chr17: 38,253,751 (T > C), rs72836608 (C > A), and rs2314339 (C > T) and Rev-erb beta Chr3:24003765 (A > G) were associated with increased serum GGT levels in obese T2DM patients. In non-obese patients, Rev-erbs SNPs had no effect on serum GGT levels. CONCLUSION: Our findings indicate that variations in the Rev-erb alpha and Rev-erb beta genes can affect metabolic changes in T2DM and these effects may vary depending on gender and obesity.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Miembro 1 del Grupo D de la Subfamilia 1 de Receptores Nucleares/genética , Polimorfismo de Nucleótido Simple , Receptores Citoplasmáticos y Nucleares/genética , Proteínas Represoras/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad
8.
PLoS One ; 15(8): e0237667, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32833960

RESUMEN

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.


Asunto(s)
Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/patología , Células Secretoras de Insulina/patología , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Obesidad/patología , Estructura Cuaternaria de Proteína , Adolescente , Animales , Línea Celular , Supervivencia Celular , Células Cultivadas , Niño , Preescolar , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Humanos , Polipéptido Amiloide de los Islotes Pancreáticos/sangre , Polipéptido Amiloide de los Islotes Pancreáticos/toxicidad , Polipéptido Amiloide de los Islotes Pancreáticos/ultraestructura , Microscopía Electrónica de Transmisión , Neuronas/efectos de los fármacos , Obesidad/sangre , Obesidad/complicaciones , Proyectos Piloto , Cultivo Primario de Células , Multimerización de Proteína , Ratas , Pruebas de Toxicidad Aguda
9.
Cell Prolif ; 53(10): e12886, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32794619

RESUMEN

OBJECTIVES: Diabetes aggravates the risk and severity of periodontitis, but the specific mechanism remains confused. Complement 3 (C3) is closely related to complications of type 2 diabetes (T2DM). In the present study, we concentrated on whether C3 mediates the development of periodontitis in T2DM. MATERIALS AND METHODS: Levels of C3 in blood and gingival crevicular fluid (GCF) of patients were measured first. A C3-knockout diabetic mouse model was established, real-time PCR, Western blotting and histological investigation were performed to evaluate the progress of periodontitis. Microcomputed tomography (micro-CT) and TRAP staining were performed to detect alveolar bone resorption. Immunofluorescence was performed to detect polarization of macrophages. RESULTS: Our data showed that C3 levels were elevated in the blood and GCF of T2DM patients compared with non-diabetic individuals. Increased C3 was closely related to the upregulation of inflammatory cytokines including interleukin (IL)-1, IL-6 and tumour necrosis factor-alpha (TNF-α), as well as the decline of the bone volume density (BMD) and bone volume over total volume (BV/TV) of the alveolar bones in diabetic mice. The deletion of C3 inhibited inflammatory cytokines and rescued the decreased BMD and BV/TV of the alveolar bones. C3-mediated polarization of macrophages was responsible for the damage. CONCLUSION: T2DM-related upregulation of C3 contributes to the development of periodontitis by promoting macrophages M1 polarization and inhibiting M2 polarization, triggering a pro-inflammatory effect on periodontal tissues.


Asunto(s)
Complemento C3/metabolismo , Diabetes Mellitus Tipo 2/patología , Macrófagos/inmunología , Periodontitis/diagnóstico , Adulto , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/patología , Proceso Alveolar/fisiología , Animales , Densidad Ósea , Complemento C3/análisis , Complemento C3/genética , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patología , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Líquido del Surco Gingival/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Activación de Macrófagos , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Periodontitis/etiología , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/metabolismo
10.
Am J Trop Med Hyg ; 103(4): 1350-1351, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32783797
11.
Life Sci ; 258: 118243, 2020 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-32791154

RESUMEN

AIMS: Although autophagy impairment is a well-established cause of muscle atrophy and P300 has recently been identified as an important regulator of autophagy, the effects of P300 on autophagy and muscle atrophy in type 2 diabetes (T2D) remain unexplored. We aimed at characterizing the role of P300 in diabetic muscle and its underlying mechanism. MAIN METHODS: Protein levels of phosphorylated P300, total P300, acetylated histone H3, LC3, p62 and myosin heavy chain, and mRNA levels of Atrogin-1 and MuRF1 were analyzed in palmitic acid (PA)-treated myotubes and db/db mice. Autophagic flux was assessed using transmission electron microscopy, immunofluorescence and mRFP-GFP-LC3 lentivirus transfection in cells. Muscle weight, blood glucose and grip strength were measured in mice. Hematoxylin and eosin (H&E) staining was performed to determine changes in muscle fiber size. To investigate the effects of P300 on autophagy and myofiber remodeling, a P300 specific inhibitor, c646, was utilized. 3-Methyladenine (3-MA) was utilized to inhibit autophagosomes formation, and chloroquine (CQ) was used to block autophagic flux. KEY FINDINGS: Phosphorylation of P300 in response to PA enhanced its activity and subsequently suppressed autophagic flux, leading to atrophy-related morphological and molecular changes in myotubes. Inhibition of P300 reestablished autophagic flux and ameliorated PA-induced myotubes atrophy. However, this effect was largely abolished by co-treatment with the autophagy inhibitor CQ. In vivo results demonstrated that inhibition of P300 partially rescued muscle wasting in db/db mice, accompanied with autophagy reactivation. SIGNIFICANCE: The findings revealed that T2D-induced overactivation of P300 contributes to muscle atrophy by blocking autophagic flux.


Asunto(s)
Autofagia/fisiología , Diabetes Mellitus Tipo 2/metabolismo , Proteína p300 Asociada a E1A/metabolismo , Atrofia Muscular/metabolismo , Animales , Línea Celular , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Proteína p300 Asociada a E1A/genética , Fuerza de la Mano/fisiología , Masculino , Ratones , Ratones Transgénicos , Atrofia Muscular/genética , Atrofia Muscular/patología , Mioblastos/metabolismo , Mioblastos/patología
12.
J Fr Ophtalmol ; 43(8): 770-773, 2020 Oct.
Artículo en Francés | MEDLINE | ID: mdl-32819735

RESUMEN

PURPOSE: To study the effect of type 2 diabetes on pupil diameter. PATIENTS AND METHODS: We carried out a case-control study at the Douala Obstetrics, Gynecology and Pediatric Hospital over a 5-month period. The cases were type 2 diabetic patients, and the controls were non-diabetic patients paired for age and gender. We studied the correlation between the duration of diabetes, fasting blood sugar and the horizontal pupil diameter. RESULTS: We included 35 patients in each group. The mean age was 56.6±10.01 years. Both groups included 17 males and 18 females. The mean duration of diabetes was 2.72±4.31 years, and the mean fasting blood sugar was 2.02±0.69g/L. The mean pupil diameter was similar in the two groups. On the right side, it was 4.75±0.73mm for controls and 4.52±0.69mm for cases (P=0.179). On the left side, it was 4.70±0.68mm and 4.42±0.73mm respectively for each group (P=0.101). The duration of diabetes was correlated to pupil diameter in the right eye (r=-0.43; P=0.01) and left eye (r=-0.45; P<0.01). No additional risk was found to be associated with diabetes for right pupil diameters (OR=0.79; P=0.33), or for left ones (OR=0.76; P=0.24). CONCLUSION: Pupil diameter is similar in diabetic and non-diabetic patients. However, the duration of diabetes appears to affect pupil diameter.


Asunto(s)
Glucemia/fisiología , Diabetes Mellitus Tipo 2/patología , Pupila/fisiología , Adulto , Anciano , Glucemia/metabolismo , Camerún/epidemiología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Retinopatía Diabética/sangre , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Reflejo Pupilar/fisiología
13.
PLoS One ; 15(7): e0236453, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32726329

RESUMEN

OBJECTIVES: To assess the potential value of some miRNAs as diagnostic biomarkers for mild cognitive impairment (MCI) among patients with type2 diabetes mellitus (T2DM) and to identify other risk factors for MCI among them. METHODS: This study enrolled 163 adults with T2DM using face to face interview. Cognitive function with its domains was assessed using Adenbrooke's Cognitive Examination III (ACE III). Lipid profile, glycated hemoglobin, and miR-128, miR-132, miR- 874, miR-134, miR-323, and miR-382 expressions, using quantitative real-time PCR, were assessed. RESULTS: MCI was detected among 59/163 (36.2%) patients with T2DM. Plasma expression of miR-132 was significantly higher in T2DM patients with MCI compared to those without MCI and to normal cognitive healthy individuals (median = 2, 1.1 and 1.2 respectively, P < 0.05. Logistic regression analysis showed that higher miR-132 expression with adjusted odds ratio (AOR): 1.2 (95% CI 1.0-1.3), female gender (AOR:2.1; 95%CI 1.0-4.3), education below postgraduate (secondary and university education with AOR: 9.5 & 19.4 respectively) were the significant predicting factors for MCI among T2DM patients. Using ROC curve, miR-132 was the only assayed miRNA that significantly differentiates T2DM patients with MCI from those with normal cognition with 72.3% sensitivity, 56.2% specificity, and 63.8% accuracy (P < 0.05). Other studied miRNAs showed lower sensitivity and specificity for detecting MCI among studied T2DM participants. CONCLUSION: MCI affects nearly one-third of adult patients with T2DM. A significantly over expression of miR-132 was detected among T2DM with MCI compared to those with normal cognition.


Asunto(s)
Biomarcadores/sangre , Disfunción Cognitiva/sangre , Diabetes Mellitus Tipo 2/sangre , MicroARNs/sangre , Adulto , Cognición/fisiología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/genética , Disfunción Cognitiva/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patología , Femenino , Hemoglobina A Glucada/genética , Humanos , Lípidos/sangre , Masculino , MicroARNs/clasificación , MicroARNs/genética , Persona de Mediana Edad , Pruebas Neuropsicológicas , Factores de Riesgo
14.
PLoS One ; 15(7): e0236603, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32706828

RESUMEN

BACKGROUND AND OBJECTIVE: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been suggested to have pancreatic beta-cell preserving effect according to studies using homeostatic model of assessment for beta-cell function (HOMA-ß). However, whether HOMA-ß is a suitable biomarker for comparisons between hypoglycemic drugs with different mechanisms of action remains unclear. Therefore, we conducted a meta-analysis to compare the effects of DPP-4 inhibitors and other classes of hypoglycemic drugs on HOMA-ß and proinsulin-to-insulin ratio (PIR). METHODS: We searched MEDLINE, CENTRAL, and Ichushi-web for the period of 1966 to May 2020. We collected randomized, controlled clinical trials in patients with type 2 diabetes mellitus comparing DPP-4 inhibitors and other classes of hypoglycemic agents [α-glucosidase inhibitors (α-GIs), glucagon-like peptide-1 (GLP-1) analogues, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, or thiazolidinediones]. Weighted mean differences and 95% confidence intervals of changes in HOMA-ß or PIR during study periods were calculated for pairwise comparisons. RESULTS: Thirty-seven and 21 relevant trials were retrieved for comparisons of HOMA-ß and PIR, respectively. HOMA-ß and PIR consistently showed superiority of DPP-4 inhibitors compared with α-GIs. Both biomarkers consistently supported inferiority of DPP-4 inhibitors compared with GLP-1 analogues. However, PIR showed inferiority of DPP-4 inhibitors compared with metformin, and superiority compared with SGLT2 inhibitors, whereas HOMA-ß showed no significant differences between DPP-4 inhibitors and the two other agents. CONCLUSION: DPP-4 inhibitors appear to be superior to α-GIs but inferior to GLP-1 analogues in preservation of beta-cell function assessed by either HOMA-ß or PIR. DPP-4 inhibitors seem to be superior to SGLT2 inhibitors but inferior to metformin on islet function assessed only by PIR. Because HOMA-ß and PIR may indicate different aspects of beta-cell function, results of beta-cell function preserving effects of hypoglycemic agents should be interpreted with caution.


Asunto(s)
Biomarcadores/metabolismo , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Hipoglucemiantes/farmacología , Células Secretoras de Insulina/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/patología , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Hipoglucemiantes/uso terapéutico , Insulina/metabolismo , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Proinsulina/metabolismo , Compuestos de Sulfonilurea/farmacología , Compuestos de Sulfonilurea/uso terapéutico , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico
15.
PLoS Genet ; 16(7): e1008903, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32678846

RESUMEN

Genome wide association studies (GWAS) of human diseases have generally identified many loci associated with risk with relatively small effect sizes. The omnigenic model attempts to explain this observation by suggesting that diseases can be thought of as networks, where genes with direct involvement in disease-relevant biological pathways are named 'core genes', while peripheral genes influence disease risk via their interactions or regulatory effects on core genes. Here, we demonstrate a method for identifying candidate core genes solely from genes in or near disease-associated SNPs (GWAS hits) in conjunction with protein-protein interaction network data. Applied to 1,381 GWAS studies from 5 ancestries, we identify a total of 1,865 candidate core genes in 343 GWAS studies. Our analysis identifies several well-known disease-related genes that are not identified by GWAS, including BRCA1 in Breast Cancer, Amyloid Precursor Protein (APP) in Alzheimer's Disease, INS in A1C measurement and Type 2 Diabetes, and PCSK9 in LDL cholesterol, amongst others. Notably candidate core genes are preferentially enriched for disease relevance over GWAS hits and are enriched for both Clinvar pathogenic variants and known drug targets-consistent with the predictions of the omnigenic model. We subsequently use parent term annotations provided by the GWAS catalog, to merge related GWAS studies and identify candidate core genes in over-arching disease processes such as cancer-where we identify 109 candidate core genes.


Asunto(s)
Enfermedad de Alzheimer/genética , Neoplasias de la Mama/genética , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Mapas de Interacción de Proteínas/genética , Enfermedad de Alzheimer/patología , Precursor de Proteína beta-Amiloide/genética , Proteína BRCA1/genética , Neoplasias de la Mama/patología , Diabetes Mellitus Tipo 2/patología , Femenino , Humanos , Insulina/genética , Polimorfismo de Nucleótido Simple/genética , Proproteína Convertasa 9/genética , Factores de Riesgo
16.
PLoS One ; 15(7): e0235335, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32628695

RESUMEN

Diabetes is associated with a dramatic mortality rate due to its vascular complications. Chronic hyperglycemia in diabetes leads to enhanced glycation of erythrocytes and oxidative stress. Even though erythrocytes play a determining role in vascular complications, very little is known about how erythrocyte structure and functionality can be affected by glycation. Our objective was to decipher the impact of glycation on erythrocyte structure, oxidative stress parameters and capacity to interact with cultured human endothelial cells. In vitro glycated erythrocytes were prepared following incubation in the presence of different concentrations of glucose. To get insight into the in vivo relevance of our results, we compared these data to those obtained using red blood cells purified from diabetics or non-diabetics. We measured erythrocyte deformability, susceptibility to hemolysis, reactive oxygen species production and oxidative damage accumulation. Altered structures, redox status and oxidative modifications were increased in glycated erythrocytes. These modifications were associated with reduced antioxidant defence mediated by enzymatic activity. Enhanced erythrocyte phagocytosis by endothelial cells was observed when cultured with glycated erythrocytes, which was associated with increased levels of phosphatidylserine-likely as a result of an eryptosis phenomenon triggered by the hyperglycemic treatment. Most types of oxidative damage identified in in vitro glycated erythrocytes were also observed in red blood cells isolated from diabetics. These results bring new insights into the impact of glycation on erythrocyte structure, oxidative damage and their capacity to interact with endothelial cells, with a possible relevance to diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Eritrocitos/patología , Productos Finales de Glicación Avanzada/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Glucemia/metabolismo , Línea Celular , Técnicas de Cocultivo , Diabetes Mellitus Tipo 2/patología , Células Endoteliales , Eriptosis , Deformación Eritrocítica , Eritrocitos/metabolismo , Hemoglobina A Glucada/análisis , Voluntarios Sanos , Hemólisis , Humanos , Estrés Oxidativo , Cultivo Primario de Células
17.
PLoS One ; 15(7): e0235640, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32730268

RESUMEN

BACKGROUND: Fluid overload is common in patients with diabetes and chronic kidney disease (DM and CKD; DMCKD) and can lead to structural and functional cardiac abnormalities including left ventricular hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD). Fluid overload represents a crucial step in the pathophysiological pathways to chronic heart failure in patients with end-stage renal disease. We evaluated the impact of fluid overload on cardiac alterations in patients with diabetes and non-dialysis-dependent CKD stage 5 (DMCKD5-ND) without intrinsic heart disease. METHODS: Bioimpedance spectroscopy, echocardiography, and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) measurement were performed in 135 consecutive patients on the same day. Patients were divided into groups by tertiles of overhydration/extracellular water (OH/ECW) per bioimpedance spectroscopy. RESULTS: Fluid balance markers including OH/ECW and NT-proBNP were significantly higher in the LVDD+LVH group. OH/ECW and its exacerbation were positively associated with the ratio between early mitral inflow and annular early diastolic velocities (E/e' ratio) and left ventricular mass index (LVMI). The prevalence of LVH progressively increased across increasing tertiles of OH/ECW. In multiple regression analyses, OH/ECW as a continuous and categorical variable was independently associated with the E/e' ratio and LVMI after adjustment for multiple confounding factors. CONCLUSIONS: Fluid overload was independently associated with LVDD and LVH in patients with DMCKD5-ND. Our study suggests that structural and functional cardiac abnormalities and volume status should be evaluated simultaneously in patients with early-stage DMCKD rather than only DMCKD5-ND, in addition to intensive blood pressure and glycemic control, regardless of evident cardiovascular disease.


Asunto(s)
Diabetes Mellitus Tipo 2/patología , Fluidoterapia , Fallo Renal Crónico/patología , Anciano , Espectroscopía Dieléctrica , Ecocardiografía , Femenino , Tasa de Filtración Glomerular , Humanos , Hipertrofia Ventricular Izquierda/epidemiología , Hipertrofia Ventricular Izquierda/patología , Fallo Renal Crónico/terapia , Modelos Lineales , Masculino , Persona de Mediana Edad , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Prevalencia , Diálisis Renal , Índice de Severidad de la Enfermedad , Disfunción Ventricular Izquierda/patología
18.
Niger J Clin Pract ; 23(7): 970-974, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32620727

RESUMEN

Background: Diabetes mellitus is one of the most common metabolic disorders with a rising prevalence. It cuts across all ages and socioeconomic status. Various skin lesions are frequently observed in diabetic patients. Aims: This study was carried out to determine the prevalence, pattern, and determinants of skin diseases in diabetic patients at the Barau Dikko Teaching Hospital, Kaduna, North West Nigeria. Materials and Methods: One hundred consecutive diabetic patients attending the clinic were included in the study. Results: Many of the patients had more than one skin condition at a time. The most prevalent skin diseases were idiopathic guttate hypomelanosis which was seen in 61% of patients, infections from fungal, bacterial, and viral causes occurred in 30% of patients, other skin disorders were diabetic dermopathy seen in 17% of patients, palmoplantar hyperpigmentation was seen in 13% of patients, while pruritus occurred in 12% of patients and xerosis was seen in 10% of patients. Conclusion: Skin disorders are common among diabetic patients at Barau Dikko Teaching Hospital, Kaduna, North West Nigeria.


Asunto(s)
Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Enfermedades de la Piel/epidemiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Instituciones de Atención Ambulatoria , Estudios Transversales , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/patología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/patología , Femenino , Hospitales de Enseñanza , Humanos , Masculino , Persona de Mediana Edad , Nigeria/epidemiología , Prevalencia , Prurito/epidemiología , Piel/patología , Adulto Joven
19.
Diabetes Res Clin Pract ; 166: 108334, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32702469

RESUMEN

AIMS: To assess sex differences in cardiovascular (CVD) risk factor changes before and after the development of type 2 diabetes, and, the association between incident diabetes with incident CVD in mid-life. METHODS: We included 4893 Coronary Artery Risk Development in Young Adults Study participants, age 18-30 years at enrollment (1985-86). We ascertained incident diabetes and assessed sex differences in annual change in body mass index, blood pressure, and lipids before and after the ascertainment of diabetes using piecewise linear regression. We examined sex differences in the association between incident diabetes with incident CVD over 31 years of median follow-up. RESULTS: Progression in most CVD risk factors did not differ by sex before diabetes. Women had better CVD profiles at the time of diabetes compared to men, and after diabetes, women had worse annual changes in blood pressure and lipids. Incident diabetes was associated with a higher hazard for incident CVD (Hazard Ratio [HR]: 1.45, 95% confidence limits: 1.07, 1.96) and we did not observe effect modification by sex (p for interaction = 0.8). CONCLUSIONS: CVD risk factors worsened more rapidly after the development of type 2 diabetes for women than men. However, diabetes was not a stronger risk factor for incident CVD for women than men.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Diabetes Mellitus Tipo 2/epidemiología , Angiopatías Diabéticas/epidemiología , Adolescente , Adulto , Edad de Inicio , Enfermedades Cardiovasculares/patología , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Angiopatías Diabéticas/patología , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo , Caracteres Sexuales , Factores de Tiempo , Adulto Joven
20.
Diab Vasc Dis Res ; 17(4): 1479164120945675, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32722929

RESUMEN

Activation of the prostaglandin E2 receptor EP4 alters polarization of adipose tissue macrophages towards the anti-inflammatory M2 phenotype to suppress chronic inflammation. However, the role of EP4 signalling in pancreatic macrophages that affect insulin secretion is unclear. We examined the role of EP4 signalling in islet inflammation in vitro and in vivo. Obese diabetic db/db mice were treated with an EP4-selective agonist or vehicle for 4 weeks. Islet morphology did not significantly differ and glucose-stimulated insulin secretion was increased, whereas the pancreatic M1/M2 ratio was decreased in the EP4 agonist-treated group compared to the vehicle group. Because EP4 activation in MIN6 cells did not affect insulin secretion, we used a MIN6/macrophage co-culture system to evaluate the role of EP4 signalling in islet inflammation and subsequent inhibition of insulin release. Co-culture with M1-polarized macrophages markedly suppressed insulin expression in MIN6 cells; however, modulation of M1 polarization by the EP4 agonist significantly reversed the negative impact of co-cultivation on insulin production. The enhanced expression levels of pro-inflammatory cytokines in co-cultured MIN6 cells were markedly inhibited by EP4 agonist treatment of M1 macrophages. Thus, EP4 activation may suppress islet inflammation and protect ß-cell function by altering inflammatory macrophages in the diabetic pancreas.


Asunto(s)
Plasticidad de la Célula , Diabetes Mellitus Tipo 2/metabolismo , Inflamación/metabolismo , Células Secretoras de Insulina/metabolismo , Macrófagos Peritoneales/metabolismo , Obesidad/metabolismo , Subtipo EP4 de Receptores de Prostaglandina E/metabolismo , Animales , Línea Celular Tumoral , Técnicas de Cocultivo , Citocinas/metabolismo , Diabetes Mellitus Tipo 2/patología , Modelos Animales de Enfermedad , Inflamación/patología , Mediadores de Inflamación/metabolismo , Insulina/metabolismo , Células Secretoras de Insulina/patología , Activación de Macrófagos , Macrófagos Peritoneales/patología , Ratones , Obesidad/patología , Fenotipo , Vías Secretoras , Transducción de Señal
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