Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55.678
Filtrar
1.
Medicine (Baltimore) ; 100(6): e23843, 2021 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-33578512

RESUMEN

BACKGROUND: Diabetes refers to any group of metabolic diseases characterized by high blood sugar and generally thought to be caused by insufficient production of insulin, impaired response to insulin. Globally, patients with type 2 diabetes account for more than 85% of the total diabetic patients, and due to factors, such as obesity, aging, environment and lifestyle, the incidence of diabetes is rising. Salvia miltiorrhiza (SM) is a medicine used to treat diabetes in China. In recent years, it has been reported that SM has the effect of improving type 2 diabetes. However, there is no systematic review of its efficacy and safety yet. Therefore, we propose a systematic review to evaluate the efficacy and safety of SM for T2D. METHODS: Six databases will be searched: China National Knowledge Infrastructure (CNKI), China Biological Medicine (CBM), China Scientific Journals Database (CSJD), Wanfang database, PubMed, and EMBASE. The information is searched from January 2010 to July 2020. Languages are limited to English and Chinese. The primary outcomes include 2 hour plasma glucose, fasting plasma glucose, hemoglobin A1c, homeostasis model assessment of insulin resistance, and fasting plasma insulin. The secondary outcomes include clinical efficacy and adverse events. RESULTS: This systematic review will evaluate the efficacy and safety of Salvia miltiorrhiza in the treatment of type 2 diabetes. CONCLUSION: This systematic review provides evidence as to whether Salvia miltiorrhiza is effective and safe for type 2 diabetes. ETHICS: Ethical approval is not necessary as this protocol is only for systematic review and does not involve in privacy data or an animal experiment. SYSTEMATIC REVIEW REGISTRATION: INPLASY2020110046.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Salvia miltiorrhiza/química , China/epidemiología , Manejo de Datos , Diabetes Mellitus Tipo 2/epidemiología , Ayuno/sangre , Femenino , Glucosa/análisis , Hemoglobina A Glucada/análisis , Homeostasis/efectos de los fármacos , Humanos , Incidencia , Insulina/sangre , Masculino , Medicina China Tradicional/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Seguridad , Resultado del Tratamiento
2.
Nat Med ; 27(1): 49-57, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33398163

RESUMEN

The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3 to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have imminent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Fenotipo , Antropometría , Glucemia/metabolismo , Composición Corporal , Estudios de Cohortes , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad
3.
Medicina (Kaunas) ; 57(1)2021 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-33466617

RESUMEN

Background and objectives: Critically and non-critically ill patients with SARS-CoV-2 infection (Covid-19) may present with higher-than-expected glycemia, even in the absence of diabetes. With this study we aimed to assess glucose, glycemic gap (GlyG) and insulin secretion/sensitivity measures in patients with Covid-19. Materials and Methods: We studied, upon admission, 157 patients with Covid-19 (84: in wards and 73: in intensive care units; ICU); 135 had no history of diabetes. We measured blood glucose upon admission as well as glycated hemoglobin (A1c), plasma insulin and C-peptide. We calculated the GlyG and the Homeostasis Model Assessment 2 (HOMA2) estimates of steady state beta cell function (HOMA2%B) and insulin sensitivity (HOMA2%S). Statistical assessment was done with analysis or the Kruskal-Wallis test. Results: Compared to patients in the wards without diabetes, patients with diabetes in the wards, as well as patients in the ICU (without or with diabetes) had higher admission glycemia. The GlyG was significantly higher in patients without diabetes in the ICU compared to patients without diabetes in the wards, while HOMA2%B based on glucose and insulin was significantly higher in the ICU patients compared to patients in the wards. Of all the parameters, HOMA2%S based on C-peptide/glucose was higher in survivors (n = 133). Conclusions: In our series of patients with Covid-19, a substantial number of patients with and without diabetes had admission hyperglycemia and those who were critically ill may have had compromised insulin secretion and lowered sensitivity to insulin. These findings lend credence to reports of association between Covid-19 and hyperglycemia/secondary diabetes.


Asunto(s)
Glucemia/análisis , Péptido C/sangre , Resistencia a la Insulina , Insulina/sangre , Anciano , Enfermedad Crítica , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Femenino , Hemoglobina A Glucada/análisis , Grecia/epidemiología , Hospitalización , Humanos , Hiperglucemia , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad
4.
Eur J Endocrinol ; 184(2): 289-298, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33513126

RESUMEN

Background: Diabetes mellitus is an established risk factor for cardiovascular diseases. Even impaired levels of glucose and insulin might harm organ function prior to diabetes onset. Whether serum glucose or insulin plays a direct role in cardiac dysfunction or lung volume reduction remains unclear. The aim was to investigate the relationship between glucose and insulin with the right ventricle and lung volumes within KORA-MRI FF4 study. Methods: From the KORA-MRI FF4 cohort study 337 subjects (mean age 55.7 ± 9.1 years; 43% women) underwent a whole-body 3T MRI scan. Cardiac parameters derived from a cine-steady-state free precession sequence using cvi42. MRI-based lung volumes derived semi-automatically using an in-house algorithm. Fasting serum glucose, fasting insulin levels, and HOMA index were calculated in all study subjects. Linear regression analyses were performed to assess the relationships between glucose and insulin levels with right ventricle volumes and lung volumes adjusted for age, sex, BMI, and cardiovascular risk factors. Results: In univariate and multivariate-adjusted models, high serum insulin was inversely associated with end-diastolic volume (ß = -12.43, P < 0.001), end-systolic volume (ß = -7.12, P < 0.001), stroke volume (ß = -5.32, P < 0.001), but not with ejection fraction. The association remained significant after additional adjustment for lung volumes. Similarly, serum insulin was inversely associated with lung volume (ß = -0.15, P = 0.04). Sensitivity analysis confirmed results after excluding subjects with known diabetes. Conclusions: Serum insulin was inversely associated with right ventricle function and lung volumes in subjects from the general population free of cardiovascular disease, suggesting that increased insulin levels may contribute to subclinical cardiopulmonary circulation impairment.


Asunto(s)
Insulina/sangre , Pulmón/patología , Función Ventricular Derecha/fisiología , Adulto , Anciano , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios de Cohortes , Femenino , Alemania , Pruebas de Función Cardíaca , Humanos , Pulmón/diagnóstico por imagen , Pulmón/fisiopatología , Mediciones del Volumen Pulmonar , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Factores de Riesgo
5.
Nat Commun ; 12(1): 24, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33402679

RESUMEN

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.


Asunto(s)
Anorexia Nerviosa/genética , Glucemia/metabolismo , Intolerancia a la Glucosa/genética , Proteínas Sustrato del Receptor de Insulina/genética , Resistencia a la Insulina/genética , Insulina/sangre , Factores de Transcripción de Tipo Kruppel/genética , Adulto , Anorexia Nerviosa/sangre , Anorexia Nerviosa/etnología , Anorexia Nerviosa/fisiopatología , Grupo de Ascendencia Continental Europea , Ayuno/sangre , Femenino , Expresión Génica , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/etnología , Intolerancia a la Glucosa/fisiopatología , Humanos , Proteínas Sustrato del Receptor de Insulina/sangre , Factores de Transcripción de Tipo Kruppel/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Caracteres Sexuales , Factores Sexuales , Relación Cintura-Cadera
6.
Phytomedicine ; 80: 153395, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33137599

RESUMEN

BACKGROUND: Curcumin is a biologically active phytochemical ingredient found in turmeric. It has several pharmacologic effects that might benefit patients with polycystic ovary syndrome (PCOS). OBJECTIVE: We hypothesized curcumin to be effective in improving blood sugar levels, insulin resistance and hyperandrogenism in individuals with PCOS. METHODS: In a randomized double-blind placebo-controlled trial, individuals with PCOS were treated with curcumin (500 mg three times daily) or placebo for 12 weeks. Primary outcome measures were fasting plasma glucose (FPG), fasting insulin (FI), sex hormone levels, and hirsutism (Ferriman-Gallwey [mFG] score). Secondary outcomes included anthropometric measurements. RESULTS: Of 72 randomized individuals, 67 completed the trial. The two groups were comparable at baseline. At the end of the study, FPG and Dehydroepiandrosterone levels had decreased significantly in the intervention group compared to control (difference of change (post-pre) between intervention and placebo groups: -4.11 mg/dL; 95% CI: -8.35, -0.35 mg/dL; p = 0.033 and -26.53 microg/dL; 95% CI: -47.99, -4.34 µg/dL; p = 0.035, respectively). We also observed a statistically non-significant increase (p = 0.082) in Estradiol levels in the intervention group compared to control. No serious adverse events were reported throughout the trial. CONCLUSIONS: Curcumin might be a safe and useful supplement to ameliorate PCOS-associated hyperandrogenemia and hyperglycemia. However, longer trials investigating different dosages in longer durations are needed to underpin these findings.


Asunto(s)
Glucemia/análisis , Curcumina/uso terapéutico , Resistencia a la Insulina , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adolescente , Adulto , Andrógenos/sangre , Deshidroepiandrosterona/sangre , Suplementos Dietéticos , Método Doble Ciego , Femenino , Hirsutismo/tratamiento farmacológico , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/etiología , Insulina/sangre , Persona de Mediana Edad , Placebos , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/complicaciones , Resultado del Tratamiento , Adulto Joven
7.
Nat Biomed Eng ; 5(1): 53-63, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33349659

RESUMEN

Biosensors that continuously measure circulating biomolecules in real time could provide insights into the health status of patients and their response to therapeutics. But biosensors for the continuous real-time monitoring of analytes in vivo have only reached nanomolar sensitivity and can measure only a handful of molecules, such as glucose and blood oxygen. Here we show that multiple analytes can be continuously and simultaneously measured with picomolar sensitivity and sub-second resolution via the integration of aptamers and antibodies into a bead-based fluorescence sandwich immunoassay implemented in a custom microfluidic chip. After an incubation time of 30 s, bead fluorescence is measured using a high-speed camera under spatially multiplexed two-colour laser illumination. We used the assay for continuous quantification of glucose and insulin concentrations in the blood of live diabetic rats to resolve inter-animal differences in the pharmacokinetic response to insulin as well as discriminate pharmacokinetic profiles from different insulin formulations. The assay can be readily modified to continuously and simultaneously measure other blood analytes in vivo.


Asunto(s)
Glucemia/análisis , Técnica del Anticuerpo Fluorescente/métodos , Insulina/sangre , Técnicas Analíticas Microfluídicas/instrumentación , Animales , Diabetes Mellitus Experimental , Diseño de Equipo , Técnica del Anticuerpo Fluorescente/instrumentación , Masculino , Ratas , Ratas Sprague-Dawley
8.
Gene ; 766: 145155, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950634

RESUMEN

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.


Asunto(s)
Adipocitos Marrones/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Epidídimo/efectos de los fármacos , Nitratos/administración & dosificación , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Epidídimo/metabolismo , Glucosa/metabolismo , Insulina/sangre , Masculino , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/genética , Ratas , Ratas Wistar , Estreptozocina/farmacología
9.
Metabolism ; 114: 154409, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33096076

RESUMEN

BACKGROUND AND OBJECTIVES: The gut-liver axis plays an important role in the pathogenesis of nonalcoholic steatohepatitis (NASH), and increased intestinal permeability causes transfer of endotoxin to the liver, which activates the immune response, ultimately leading to hepatic inflammation. Nuclear receptor Rev-erbα is a critical regulator of circadian rhythm, cellular metabolism, and inflammatory responses. However, the role and mechanism of Rev-erbα in gut barrier function and NASH remain unclear. In the present study, we investigated the involvement of Rev-erbα in the regulation of intestinal permeability and the treatment of NASH. METHODS AND RESULTS: The expression of tight junction-related genes and Rev-erbs decreased in the jejunum, ileum and colon of mice with high cholesterol, high fat diet (CL)-induced NASH. Chromatin immunoprecipitation analysis indicated that REV-ERBα directly bound to the promoters of tight junction genes to regulate intestinal permeability. Pharmacological activation of REV-ERBα by SR9009 protected against lipopolysaccharide-induced increased intestinal permeability both in vitro and in vivo, and these effects were associated with the activation of autophagy and decreased apoptotic signaling of epithelial cells. In addition, the chronopharmacological effects of SR9009 were more potent at Zeitgeber time 0 (ZT0) than at ZT12, which was contrary to the rhythm of Rev-erbs in the gastrointestinal tract. The administration of SR9009 attenuated hepatic lipid accumulation, insulin resistance, inflammation, and fibrosis in mice with CL diet-induced NASH, which might be partly attributed to the enhancement of intestinal barrier function. CONCLUSION: Chronopharmacological activation of REV-ERBα might be a potential strategy to treat intestinal barrier dysfunction-related disorders and NASH.


Asunto(s)
Mucosa Intestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Pirrolidinas/uso terapéutico , Receptores Citoplasmáticos y Nucleares/agonistas , Proteínas Represoras/agonistas , Tiofenos/uso terapéutico , Uniones Estrechas/efectos de los fármacos , Animales , Autofagia/efectos de los fármacos , Glucemia , Células CACO-2 , Colesterol/sangre , Humanos , Insulina/sangre , Mucosa Intestinal/metabolismo , Hígado/metabolismo , Masculino , Ratones , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Permeabilidad/efectos de los fármacos , Pirrolidinas/farmacología , Receptores Citoplasmáticos y Nucleares/metabolismo , Proteínas Represoras/metabolismo , Transducción de Señal/efectos de los fármacos , Tiofenos/farmacología , Uniones Estrechas/metabolismo , Triglicéridos/sangre
10.
Medicine (Baltimore) ; 99(40): e22337, 2020 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-33019410

RESUMEN

At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of ß-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.


Asunto(s)
Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Ayuno/metabolismo , Resistencia a la Insulina/fisiología , Adolescente , Adulto , Péptido C/sangre , Niño , Femenino , Fructosamina/sangre , Hemoglobina A Glucada/análisis , Índice Glucémico , Humanos , Insulina/sangre , Masculino , Albúmina Sérica/análisis , Adulto Joven
11.
Medicine (Baltimore) ; 99(35): e21654, 2020 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-32871878

RESUMEN

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.


Asunto(s)
Glucemia/metabolismo , Diabetes Gestacional/sangre , Vitamina D/análogos & derivados , Adulto , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , China , Colesterol/sangre , Estudios Transversales , Femenino , Hemoglobina A Glucada/metabolismo , Humanos , Insulina/sangre , Resistencia a la Insulina , Embarazo , Triglicéridos/sangre , Factor de Necrosis Tumoral alfa/sangre , Vitamina D/sangre
12.
High Blood Press Cardiovasc Prev ; 27(6): 515-526, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32964344

RESUMEN

Epidemiological studies have documented a high incidence of diabetes in hypertensive patients.Insulin resistance is defined as a less than expected biologic response to a given concentration of the hormone and plays a pivotal role in the pathogenesis of diabetes. However, over the last decades, it became evident that insulin resistance is not merely a metabolic abnormality, but is a complex and multifaceted syndrome that can also affect blood pressure homeostasis. The dysregulation of neuro-humoral and neuro-immune systems is involved in the pathophysiology of both insulin resistance and hypertension. These mechanisms induce a chronic low grade of inflammation that interferes with insulin signalling transduction. Molecular abnormalities associated with insulin resistance include the defects of insulin receptor structure, number, binding affinity, and/or signalling capacity. For instance, hyperglycaemia impairs insulin signalling through the generation of reactive oxygen species, which abrogate insulin-induced tyrosine autophosphorylation of the insulin receptor. Additional mechanisms have been described as responsible for the inhibition of insulin signalling, including proteasome-mediated degradation of insulin receptor substrate 1/2, phosphatase-mediated dephosphorylation and kinase-mediated serine/threonine phosphorylation of both insulin receptor and insulin receptor substrates. Insulin resistance plays a key role also in the pathogenesis and progression of hypertension-induced target organ damage, like left ventricular hypertrophy, atherosclerosis and chronic kidney disease. Altogether these abnormalities significantly contribute to the increase the risk of developing type 2 diabetes.


Asunto(s)
Presión Sanguínea , Diabetes Mellitus Tipo 2/fisiopatología , Hipertensión Esencial/fisiopatología , Resistencia a la Insulina , Animales , Biomarcadores/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/epidemiología , Hipertensión Esencial/sangre , Hipertensión Esencial/epidemiología , Humanos , Incidencia , Insulina/sangre , Pronóstico , Factores de Riesgo , Transducción de Señal
13.
PLoS One ; 15(9): e0239506, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32976523

RESUMEN

BACKGROUND: Low carnitine status may underlie the development of insulin resistance and metabolic inflexibility. Intravenous lipid infusion elevates plasma free fatty acid (FFA) concentration and is a model for simulating insulin resistance and metabolic inflexibility in healthy, insulin sensitive volunteers. Here, we hypothesized that co-infusion of L-carnitine may alleviate lipid-induced insulin resistance and metabolic inflexibility. METHODS: In a randomized crossover trial, eight young healthy volunteers underwent hyperinsulinemic-euglycemic clamps (40mU/m2/min) with simultaneous infusion of saline (CON), Intralipid (20%, 90mL/h) (LIPID), or Intralipid (20%, 90mL/h) combined with L-carnitine infusion (28mg/kg) (LIPID+CAR). Ten volunteers were randomized for the intervention arms (CON, LIPID and LIPID+CAR), but two dropped-out during the study. Therefore, eight volunteers participated in all three intervention arms and were included for analysis. RESULTS: L-carnitine infusion elevated plasma free carnitine availability and resulted in a more pronounced increase in plasma acetylcarnitine, short-, medium-, and long-chain acylcarnitines compared to lipid infusion, however no differences in skeletal muscle free carnitine or acetylcarnitine were found. Peripheral insulin sensitivity and metabolic flexibility were blunted upon lipid infusion compared to CON but L-carnitine infusion did not alleviate this. CONCLUSION: Acute L-carnitine infusion could not alleviated lipid-induced insulin resistance and metabolic inflexibility and did not alter skeletal muscle carnitine availability. Possibly, lipid-induced insulin resistance may also have affected carnitine uptake and may have blunted the insulin-induced carnitine storage in muscle. Future studies are needed to investigate this.


Asunto(s)
Carnitina/administración & dosificación , Ácidos Grasos no Esterificados/sangre , Ácidos Grasos no Esterificados/metabolismo , Resistencia a la Insulina/fisiología , Lípidos/administración & dosificación , Adulto , Carnitina/análogos & derivados , Carnitina/sangre , Estudios Cruzados , Emulsiones/administración & dosificación , Humanos , Bombas de Infusión , Insulina/sangre , Insulina/metabolismo , Masculino , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fosfolípidos/administración & dosificación , Aceite de Soja/administración & dosificación , Adulto Joven
14.
PLoS One ; 15(9): e0238522, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32946478

RESUMEN

The effects of feeding frequency on postprandial response of circulating appetite-regulating hormones, insulin, glucose and amino acids, and on physical activity, energy expenditure, and respiratory quotient were studied in healthy adult cats. Two experiments were designed as a 2 x 3 replicated incomplete Latin square design. Eight cats, with an average body weight (BW) of 4.34 kg ± 0.04 and body condition score (BCS) of 5.4 ± 1.4 (9 point scale), were fed isocaloric amounts of a commercial adult maintenance canned cat food either once (0800 h) or four times daily (0800 h, 1130 h, 1500 h, 1830 h). Study 1 consisted of three 21-d periods. On day 14, two fasted and 11 postprandial blood samples were collected over 24 hours to measure plasma concentrations of ghrelin, GLP-1, GIP, leptin, PYY, insulin and amino acids, and whole blood glucose. Physical activity was monitored from day 15 to 21 of each period. In Study 2 indirect calorimetry was performed on the last day of each period. Body weight was measured weekly and feed intake recorded daily in both experiments. No effect of feeding regimen on BW was detected. Cats eating four times daily had lesser plasma concentrations of GIP and GLP-1 (P<0.05) and tended to have lesser plasma PYY concentrations (P<0.1). Plasma leptin and whole blood glucose concentrations did not differ between regimens (P>0.1). Cats fed once daily had a greater postprandial plasma amino acid response, and greater plasma ghrelin and insulin concentrations (P<0.05). Physical activity was greater in cats fed four times (P<0.05), though energy expenditure was similar between treatments at fasting and in postprandial phases. Finally, cats eating one meal had a lower fasting respiratory quotient (P<0.05). Overall, these data indicate that feeding once a day may be a beneficial feeding management strategy for indoor cats to promote satiation and lean body mass.


Asunto(s)
Aminoácidos/metabolismo , Regulación del Apetito , Gatos/fisiología , Conducta Alimentaria , Hormonas/metabolismo , Aminoácidos/sangre , Alimentación Animal/análisis , Animales , Apetito , Glucemia/análisis , Glucemia/metabolismo , Gatos/sangre , Metabolismo Energético , Femenino , Ghrelina/sangre , Ghrelina/metabolismo , Hormonas/sangre , Insulina/sangre , Insulina/metabolismo , Masculino , Fotoperiodo , Condicionamiento Físico Animal , Respiración
15.
Open Heart ; 7(2)2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32938758

RESUMEN

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.


Asunto(s)
Infecciones por Coronavirus/terapia , Dieta Baja en Carbohidratos , Suplementos Dietéticos , Hiperinsulinismo/terapia , Insulina/sangre , Magnesio/uso terapéutico , Neumonía Viral/terapia , Trombosis/terapia , Vitamina D/uso terapéutico , Betacoronavirus/patogenicidad , Biomarcadores/sangre , Glucemia/metabolismo , Infecciones por Coronavirus/sangre , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/virología , Suplementos Dietéticos/efectos adversos , Interacciones Huésped-Patógeno , Humanos , Hiperinsulinismo/sangre , Hiperinsulinismo/epidemiología , Cetonas/sangre , Magnesio/sangre , Pandemias , Neumonía Viral/sangre , Neumonía Viral/epidemiología , Neumonía Viral/virología , Pronóstico , Factores de Riesgo , Trombosis/sangre , Trombosis/epidemiología , Trombosis/virología , Vitamina D/sangre , Zinc/uso terapéutico
16.
Intern Med ; 59(18): 2229-2235, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32938850

RESUMEN

Objective The measurement of C-peptide immunoreactivity (CPR) is essential for evaluating the pancreatic ß-cell function and selecting appropriate therapeutic agents in patients with diabetes mellitus. The meal tolerance test (MTT) is simple to administer physiological insulin-stimulating test. Previous studies have reported that several CPR-related indices are useful markers for predicting insulin requirement in type 2 diabetes. In the present study, we investigated the serum CPR response during the MTT in hospitalized patients with type 2 diabetes mellitus in order to clarify the clinical utility of the MTT. Methods We performed the MTT using a test meal with timed measurements of the serum CPR level based on the oral glucose tolerance test over 180 minutes and tested the correlation of various CPR-related indices and clinical factors in patients with type 2 diabetes mellitus. Patients The subjects were patients with type 2 diabetes mellitus who had been admitted to our hospital for diabetes management and education. The final study population consisted of 68 patients. Results The fasting CPR level was correlated with the 24-hour urinary CPR excretion and body mass index. The serum CPR level at 120 minutes in the MTT was strongly correlated with the area under the curve of CPR during the MTT. The patients who needed insulin therapy at 6 months after hospitalization showed a significant lower incremental CPR value from 0 to 120 minutes in the MTT than those who did not need insulin therapy. Conclusion The plasma C-peptide levels at 0 and 120 minutes in the MTT provide essential information for the clinical management of patients with type 2 diabetes mellitus.


Asunto(s)
Péptido C/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Técnicas de Diagnóstico Endocrino , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Adulto , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Células Secretoras de Insulina/fisiología , Masculino , Comidas , Carne , Persona de Mediana Edad , Periodo Posprandial
17.
Life Sci ; 260: 118432, 2020 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-32941895

RESUMEN

AIMS: Biological, psychosocial and lifestyle risk factors interact in the development of type 2 diabetes mellitus (T2DM). To date, the effects of sex, chronic stress (CS) and high-fat diet (HFD) on T2DM and the ability of linalyl acetate (LA) to prevent T2DM have not been determined. This study therefore explored the differential effects of CS and HFD on T2DM, as well as the ability of LA to prevent T2DM development, in male and female rats. MAIN METHODS: T2DM was induced in rats by feeding an HFD and placing them under immobilization stress for 2 h/day for 3 weeks. Low-dose streptozotocin was administered on day 15, and LA was administered for 3 weeks. KEY FINDINGS: Fasting blood sugar (FBS) increased in HFD-fed male, but not female, rats. CS further increased FBS in HFD-fed rats, whereas CS alone did not alter FBS. The homeostatic model assessment-insulin resistance (HOMA-IR) showed results similar to FBS. Serum corticosterone levels markedly increased only in HFD-fed male rats exposed to CS. Pancreas nuclear factor kappa B (NF-κB) levels were higher in HFD-fed male rats exposed to CS than in control rats although there were no sex differences. LA 10 mg/kg significantly reduced FBS, serum insulin, HOMA-IR, and serum corticosterone levels in HFD-fed male rats exposed to CS. LA 10 mg/kg also tended to reduce NF-κB in the pancreas and significantly increased mitochondrial membrane potential (MMP) in the liver. SIGNIFICANCE: Male rats are vulnerable to T2DM induced by CS and HFD, and LA can prevent T2DM in these rats not only by reducing insulin resistance and corticosterone levels but by increasing MMP in the liver.


Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Monoterpenos/farmacología , Animales , Corticosterona/sangre , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/prevención & control , Diabetes Mellitus Tipo 2/etiología , Dieta Alta en Grasa/efectos adversos , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Hipoglucemiantes/farmacología , Insulina/sangre , Masculino , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratas Sprague-Dawley , Factores Sexuales , Estreptozocina/administración & dosificación , Estreptozocina/toxicidad , Estrés Fisiológico
18.
PLoS One ; 15(9): e0238095, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32881889

RESUMEN

PURPOSE: Diabetes mellitus is a kind of highly prevalent chronic disease in the world. The intervention measures on the risk factors of prediabetes contribute to control and reduce the occurrence of diabetes. This study aimed to investigate the correlation between proinsulin (PI), true insulin (TI), PI/TI, 25(OH) D3, waist circumference (WC), and risk of prediabetes. METHODS: In this cross-sectional study, 1662 subjects including 615 prediabetes and 1047 non-prediabetes were recruited. Spearman's correlation analysis was used to explore the association of PI, TI, PI/TI, 25(OH) D3, and waist circumference with prediabetes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Receiver-Operator Characteristic (ROC) curve was used to evaluate the risk of prediabetes. RESULTS: Our study showed that FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC could enhance the risk of prediabetes (OR 1.034; OR 1.007; OR 1.005; OR 1.002; OR 3.577, OR 1.053, respectively; all p< 0.001). Stratified analyses indicated that FPI/FTI associated with an increased risk of prediabetes in men (OR 2.080, p = 0.042). FTI have a weak association with prediabetes risk in men and women (OR 0.987, p = 0.001; OR 0.994, p = 0.004, respectively). 2hPI could decrease prediabetes in women (OR 0.995, p = 0.037). Interesting, the sensitivity (86.0%) and AUC (0.942, p< 0.001) of combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) were higher than the diagnostic value of these alone diagnoses. The optimal cutoff point of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC for indicating prediabetes were 15.5 mU/l, 66.5 mU/l, 71.5 mU/l, 460.5 mU/l, 35.5 ng/ml, and 80.5 cm, respectively. What's more, the combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) significantly improved the diagnostic value beyond the alone diagnoses of prediabetes in men and women (AUC 0.771; AUC 0.760, respectively). CONCLUSION: The FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC significantly associated with an increased risk of prediabetes. The combination of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC might be used as diagnostic indicators for prediabetes.


Asunto(s)
Calcifediol/sangre , Insulina/sangre , Estado Prediabético/diagnóstico , Proinsulina/sangre , Adulto , Anciano , Área Bajo la Curva , China , Estudios Transversales , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina Regular Humana , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Curva ROC , Factores de Riesgo , Circunferencia de la Cintura
19.
DNA Cell Biol ; 39(11): 2005-2016, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32986505

RESUMEN

Background and Aims: Exosomes contain numerous RNAs and transfer them between cells or organs, thereby establishing intercellular or interorgan communication. The roles of mRNAs and long noncoding RNAs (lncRNAs) from umbilical cord blood exosomes in gestational diabetes mellitus (GDM) occurrence and fetus growth remain poorly understood. We aimed to establish the differential mRNA and lncRNA expression profiles in umbilical cord blood exosomes from GDM patients compared with normal controls. Results: Using microarray technology, we identified 84 mRNAs and 256 lncRNAs as differentially expressed in umbilical cord blood exosomes of GDM patients compared with controls. The protein-protein interaction network revealed that the differentially expressed mRNAs were associated with glucagon signaling pathway, an important GDM-related pathway. Gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analyses were performed for mRNAs associated with differentially expressed lncRNAs. The results indicated that metabolic process, growth, and development were significantly enriched, which are important in GDM development and fetus growth. Moreover, pathway network was constructed to reveal the key pathways in GDM, such as metabolic pathways and insulin signaling pathway. Further lncRNA/miRNA interaction analysis showed that most of the exosomal lncRNAs harbored miRNA binding sites, and some were associated with GDM. Conclusion: These results showed that exosomal mRNAs and lncRNAs are aberrantly expressed in the umbilical cord blood of GDM patients and play potential roles in GDM development and fetus growth.


Asunto(s)
Diabetes Gestacional/sangre , ARN Largo no Codificante/sangre , ARN Mensajero/sangre , Transcriptoma/genética , Adulto , Diabetes Gestacional/genética , Diabetes Gestacional/patología , Exosomas/genética , Femenino , Sangre Fetal/metabolismo , Humanos , Recién Nacido , Insulina/sangre , MicroARNs/sangre , Análisis por Micromatrices , Embarazo , Transducción de Señal/genética
20.
J Anim Sci ; 98(9)2020 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-32835365

RESUMEN

Activation of the mechanistic target of rapamycin (mTOR)-controlled anabolic signaling pathways in skeletal muscle of rodents and humans is responsive to the level of dietary protein supply, with maximal activation and rates of protein synthesis achieved with 0.2 to 0.4 g protein/kg body weight (BW). In horses, few data are available on the required level of dietary protein to maximize protein synthesis for maintenance and growth of skeletal muscle. To evaluate the effect of dietary protein level on muscle mTOR pathway activation, five mares received different amounts of a protein supplement that provided 0, 0.06, 0.125, 0.25, or 0.5 g of crude protein (CP)/kg BW per meal in a 5 × 5 Latin square design. On each sample day, horses were fasted overnight and were fed only their protein meal the following morning. A preprandial (0 min) and postprandial (90 min) blood sample was collected and a gluteus medius muscle sample was obtained 90 min after feeding the protein meal. Blood samples were analyzed for glucose, insulin, and amino acid concentrations. Activation of mTOR pathway components (mTOR and ribosomal protein S6 [rpS6]) in the muscle samples was measured by Western immunoblot analysis. Postprandial plasma glucose (P = 0.007) and insulin (P = 0.09) showed a quadratic increase, while total essential amino acid (P < 0.0001) concentrations increased linearly with the graded intake of the protein supplement. Activation of mTOR (P = 0.02) and its downstream target, rpS6 (P = 0.0008), increased quadratically and linearly in relation to the level of protein intake, respectively. Comparisons of individual doses showed no differences (P > 0.05) between the 0.25 and 0.5 g of protein intake for either mTOR or rpS6 activation, indicating that protein synthesis may have reached near maximal capacity around 0.25 g CP/kg BW. This is the first study to show that the activation of muscle protein synthetic pathways in horses is dose-dependent on the level of protein intake. Consumption of a moderate dose of high-quality protein resulted in near maximal muscle mTOR pathway activation in mature, sedentary horses.


Asunto(s)
Proteínas en la Dieta/análisis , Suplementos Dietéticos/análisis , Caballos/fisiología , Biosíntesis de Proteínas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Animales , Glucemia/análisis , Dieta/veterinaria , Ayuno , Femenino , Insulina/sangre , Proteínas Musculares/metabolismo , Músculo Esquelético/efectos de los fármacos , Periodo Posprandial/efectos de los fármacos , Distribución Aleatoria
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA