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1.
Nat Commun ; 12(1): 102, 2021 01 04.
Artículo en Inglés | MEDLINE | ID: mdl-33397994

RESUMEN

Pro-inflammatory activation of adipose tissue macrophages (ATMs) is causally linked to obesity and obesity-associated disorders. A number of studies have demonstrated the crucial role of mitochondrial metabolism in macrophage activation. However, there is a lack of pharmaceutical agents to target the mitochondrial metabolism of ATMs for the treatment of obesity-related diseases. Here, we characterize a near-infrared fluorophore (IR-61) that preferentially accumulates in the mitochondria of ATMs and has a therapeutic effect on diet-induced obesity as well as obesity-associated insulin resistance and fatty liver. IR-61 inhibits the classical activation of ATMs by increasing mitochondrial complex levels and oxidative phosphorylation via the ROS/Akt/Acly pathway. Taken together, our findings indicate that specific enhancement of ATMs oxidative phosphorylation improves chronic inflammation and obesity-related disorders. IR-61 might be an anti-inflammatory agent useful for the treatment of obesity-related diseases by targeting the mitochondria of ATMs.


Asunto(s)
Tejido Adiposo/metabolismo , Sistemas de Liberación de Medicamentos , Macrófagos/metabolismo , Mitocondrias/metabolismo , Obesidad/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Animales , Peso Corporal/efectos de los fármacos , Hígado Graso/genética , Hígado Graso/patología , Inflamación/genética , Inflamación/patología , Resistencia a la Insulina , Hígado/metabolismo , Hígado/patología , Activación de Macrófagos/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Obesidad/genética , Obesidad/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , ARN Mensajero/genética , ARN Mensajero/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Pérdida de Peso/efectos de los fármacos
2.
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
3.
Phytomedicine ; 80: 153388, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33113501

RESUMEN

BACKGROUND: Insulin resistance (IR) and lipotoxicity were evidenced as the major nonalcoholic steatohepatitis (NASH) initiators. However, absence of the effective treatment against NASH progression raised our aim to discover a new promising insulin modulator and NSH preventer. PURPOSE: Our study aimed to extract and prepare a nitriles rich fraction (NRF) from Diceratella elliptica (DC.) Jonsell, investigate its insulin-sensitizing & anti-NASH potentialities and address its molecular targets in IR-NASH pathogenesis. STUDY DESIGN: NRF was prepared using natural autolysis method and compounds were identified. Then, seventy male Wistar rats were feed high fat diet (HFD) or normal pellets for 35 days. In day 14th, HFD rats were injected by Streptozotocin (STZ) once and treatment was started in day 21st with either NRF (30, 60 and 120 mg/kg; orally) or pioglitazone (PioG) (10 mg/kg; i.p) beside HFD. While, NRF-alone rats were treated with NRF (120 mg/kg; orally) beside the normal pellets. Body weight, glucose homeostasis, hepatopathological examinations were performed. METHODS: Gas liquid chromatography-mass spectrophotometry (GLC/MS) was used for compounds' identification while spectrophotometer was used for total glucosinolates (GLS) quantification. Also, the biochemical and molecular investigations concerned with liver lipotoxicity, oxidative stress, inflammation and insulin signaling pathway were investigated and confirmed with the computational prediction of the major compounds' targets. RESULTS: Butenyl and benzyl GLS were the major along with other volatile compounds. NRF had significantly increased the insulin sensitivity and improved NASH-hisptopathology showing hepatoprotective effect. While, the fraction's anti-NASH potentiality was evidenced in the normalized hepatic steatosis markers, inflammation and oxidative stress key transcriptional factors resulting in induction of insulin receptor substrates (IRSs) phosphorylation and its downstream effectors. CONCLUSION: NRF has reversed IR, stimulated leptin secretion and prevented NASH initiation showing promising anti-NASH and anti-fibrotic effects.


Asunto(s)
Brassicaceae/química , Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico/prevención & control , Extractos Vegetales/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Glucosinolatos/análisis , Leptina/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Masculino , Factor 2 Relacionado con NF-E2/metabolismo , FN-kappa B/antagonistas & inhibidores , FN-kappa B/metabolismo , Nitrilos/química , Nitrilos/farmacología , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Estrés Oxidativo/efectos de los fármacos , Pioglitazona/farmacología , Extractos Vegetales/química , Ratas Wistar , Transducción de Señal
4.
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
5.
Life Sci ; 264: 118637, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33203524

RESUMEN

AIMS: To evaluate the effects of a high-fat diet (HFD) on the progression of apical periodontitis (AP), local inflammation, systemic antioxidant status, and blood lipid profile in rats. MAIN METHODS: Sixteen male Wistar rats were fed a standard diet (SD) or a HFD. At the sixth experimental week, the pulp chambers of the mandibular first molars were exposed to develop AP. A glucose tolerance test was performed the week before euthanasia. At the tenth experimental week, the animals were euthanized and the livers were collected to estimate catalase (CAT) and reduced glutathione (GSH) levels. Blood was acquired for biochemical analysis. The size of AP was estimated from radiographs and described as AP size-to-body weight ratio; inflammatory grade of AP was determined by histological analysis. KEY FINDINGS: At the end of the experimental period, the rats fed the HFD had 30% less weight (P < 0.0001) and higher blood glucose levels after 30 min of sucrose intake (P < 0.05) than those fed the SD. Animals from the HFD group had lower levels of CAT (P < 0.01), but the same was not observed in the GSH levels. Plasma insulin and total cholesterol were not affected by the diet. The rats fed the HFD presented greater AP than those fed the SD (P < 0.05). However, the local inflammatory infiltrate was similar in both groups. SIGNIFICANCE: The alterations promoted by the consumption of a HFD were not only observed systemically, but also locally, producing greater AP in rats than a SD.


Asunto(s)
Antioxidantes/metabolismo , Dieta Alta en Grasa , Hígado/enzimología , Animales , Catalasa/metabolismo , Prueba de Tolerancia a la Glucosa , Glutatión/metabolismo , Inflamación , Resistencia a la Insulina , Lípidos/sangre , Masculino , Estrés Oxidativo , Ratas , Ratas Wistar
6.
J Steroid Biochem Mol Biol ; 205: 105770, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33065278

RESUMEN

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with acute respiratory distress syndrome and infected patients have a relatively high risk of death. Emerging risk factors for poor outcome in this disease include age, male gender, cardiovascular co-morbidities including hypertension, prior cardiovascular disease, diabetes and more recently obesity. To date there are no data relating to SARS-CoV-2 in PCOS women. The present Clinical Opinion represents a summary of the epidemiological evidence and possible pathophysiological mechanisms regarding PCOS and COVID-19. PCOS women could be more susceptible to infections compared to non-PCOS women. Insulin resistance and the associated hyperinsulinaemia are drivers for enhanced steroidogenesis in women with PCOS. Weight-gain and obesity, through their worsening effects on insulin resistance, thereby drive enhanced steroidogenesis and hyperandrogenism. All these features represent key points to provide an explanation for the possible association between PCOS and SARS-CoV-2. Indeed, androgens may drive clinical results in COVID-19, through the expression of TMPRSS2, a cellular co-receptor necessary for SARS-CoV-2 infection and through androgen-mediated immune modulation. In women with PCOS the endocrine-immune axis leads to immune dysfunction with a state of chronic inflammation, and hyperandrogenism and IR with compensatory hyperglycaemia could play a determining role in the pathophysiogenesis of the infection. However, it is possible that only specific PCOS phenotypes may be more susceptible. In addition, vitamin D deficiency and gut dysbiosis are another important factor potentially involved in the increased risk of developing severe forms of COVID-19 in PCOS women. Further scientific investigations are needed with the aim of understanding which women are most at risk of becoming infected or developing complications, what are the causal mechanisms on which it is possible to intervene with prophylactic and therapeutic measures and what the long-term consequences will be on the health of these patients.


Asunto(s)
/epidemiología , Inflamación/epidemiología , Síndrome del Ovario Poliquístico/epidemiología , Adulto , /genética , Femenino , Humanos , Hiperandrogenismo/complicaciones , Hiperandrogenismo/epidemiología , Hiperandrogenismo/genética , Hiperandrogenismo/virología , Inflamación/complicaciones , Inflamación/genética , Inflamación/virología , Resistencia a la Insulina/genética , Ovario/metabolismo , Ovario/patología , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/genética , Síndrome del Ovario Poliquístico/virología , Factores de Riesgo , /patogenicidad
7.
Food Chem ; 335: 127513, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32745838

RESUMEN

Zhenjiang aromatic vinegar is a famous traditional fermented cooking ingredient in China, with multiple nutritional and medicinal applications. Zhenjiang aromatic vinegar extract (100-400 µg/mL) is rich in polyphenols increased the glucose uptake and glucose consumption in high glucose-induced insulin resistant HepG2 (IR-HepG2) cells. Zhenjiang aromatic vinegar extract enhanced glycogen synthesis and attenuated gluconeogenesis by regulating key enzymes in IR-HepG2 cells. In addition, Zhenjiang aromatic vinegar extract ameliorated high glucose-induced IR by inhibiting phosphorylated insulin receptor substrate-1 (IRS-1) expression and activating phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway in IR-HepG2 cells. Moreover, Zhenjiang aromatic vinegar extract reduced reactive oxygen species generation and phosphorylated c-Jun NH2 terminal kinase (JNK) expression in IR-HepG2 cells. The attenuation of the high glucose is owned to the PI3K/Akt pathway activation, glycogen synthesis induction and gluconeogenesis suppression in IR-HepG2 cells.


Asunto(s)
Ácido Acético/farmacología , Glucosa/farmacología , Resistencia a la Insulina , Polifenoles/análisis , Transducción de Señal/efectos de los fármacos , Ácido Acético/química , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Proteínas Sustrato del Receptor de Insulina/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo
8.
Life Sci ; 264: 118661, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33121986

RESUMEN

Obesity and diabetes are the two major metabolic complications linked with bad eating habits and the sedentary (lazy) lifestyle. In the worst-case situation, metabolic problems are a causative factor for numerous other conditions. There is also an increased demand to control the emergence of such diseases. Dietary and lifestyle improvements contribute to their leadership at an elevated level. The present review, therefore, recommends the use of the ketogenic diet (KD) in obesity and diabetes treatment. The KD involves a diet that replaces glucose sugar with ketone bodies and is effective in numerous diseases, such as metabolic disorders, epileptic seizures, autosomal dominant polycystic disease of the kidney, cancers, peripheral neuropathy, and skeletal muscle atrophy. A lot of high profile pathways are available for KD action, including sustaining the metabolic actions on glucose sugar, suppressing insulin-like growth factor-1 (IGF1) and phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathways, altering homeostasis of the systemic ketone bodies, contributing to lowering diabetic hyperketonemia, and others. The KD regulates the level of glucose sugar and insulin and can thus claim to be an effective diabetes approach. Thus, a stopgap between obesity and diabetes treatment can also be evidenced by KD.


Asunto(s)
Diabetes Mellitus/dietoterapia , Diabetes Mellitus/prevención & control , Dieta Cetogénica , Obesidad/dietoterapia , Obesidad/prevención & control , Animales , Diabetes Mellitus/epidemiología , Humanos , Resistencia a la Insulina , Obesidad/epidemiología
9.
Food Chem ; 340: 128169, 2021 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-33007695

RESUMEN

Polyphenols from cambuci (CBC) (Campomanesia phaea (O. Berg.)), a Brazilian native fruit, were investigated on therapeutic actions mitigating insulin resistance and hepatic steatosis in high-fat-sucrose diet (HFS) induced obese mice. For this, C57BL/6J mice fed with a obesogenic and diabetogenic HFS diet were administered with either water or two CBC doses (36 or 74 mg gallic acid equivalent (GAE)/kg body weight) by gavage from week 6 to week 14 (end-point) of HFS feeding. CBC reduced body weight gain, inflammation, hepatic steatosis, hyperglycemia, glucose intolerance, and insulin resistance in liver and skeletal muscle of obese mice, and such effects were associated with activation of Akt and AMPK in these tissues. In conclusion, polyphenols from CBC show important therapeutic actions ameliorating obesity-associated complications.


Asunto(s)
Resistencia a la Insulina , Myrtaceae/química , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Obesidad/complicaciones , Polifenoles/farmacología , Animales , Dieta Alta en Grasa/efectos adversos , Frutas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/inducido químicamente , Obesidad/metabolismo , Polifenoles/uso terapéutico
10.
Life Sci ; 264: 118615, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33096115

RESUMEN

Non-alcoholic fatty liver disease (NFLD) is one of the present public health problems which have no specific and effective treatment. The speed of the disease progression depends on the patient's lifestyle. Due to life stresses and lack of time, a high number of people depend on fast food containing a high amount of fats which one of the main causes of insulin resistance (IR). IR is one of the metabolic disorders which strongly intersected with molecular NAFLD and leading to its progression into non-alcoholic steatohepatitis (NASH). In this review, we introduced the updated statistics of NAFLD and NASH progression all over the world shows its importance, etiologies, and pathogenesis. Also, IR and its role in NASH initiation and progression explored, and current treatments with its limitations have been explained. Glucosinolates (GLS) is a group of phytochemicals which known by its potent hydrolysis products with promising anti-cancer effect. In this review, we have collected the recent experimental studies of different GLS hydrolysis products against IR and chronic liver diseases supported by our lab finding. Finally, we recommend this group of phytochemicals as promising molecules to be studied experimentally and clinically against a wide range of chronic liver diseases with an acceptable safety margin.


Asunto(s)
Glucosinolatos/administración & dosificación , Resistencia a la Insulina/fisiología , Enfermedad del Hígado Graso no Alcohólico/dietoterapia , Fitoquímicos/administración & dosificación , Conducta de Reducción del Riesgo , Grasas de la Dieta/efectos adversos , Grasas de la Dieta/metabolismo , Femenino , Glucosinolatos/metabolismo , Humanos , Hidrólisis , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Fitoquímicos/metabolismo
11.
Life Sci ; 264: 118618, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33141040

RESUMEN

AIMS: Obesity represents a global health problem. Excessive caloric intake promotes the release of inflammatory mediators by hypertrophic adipocytes and obesity-induced inflammation is now recognized as a risk factor for the development of several diseases, such as cardiovascular diseases, insulin resistance, type-II diabetes, liver steatosis and cancer. Since obesity causes inflammation, we tested the ability of acetylsalicylic acid (ASA), a potent anti-inflammatory drug, in counteracting this inflammatory process and in mitigating obesity-associated health complications. MAIN METHODS: Mice were fed with standard (SD) or high fat diet (HFD) for 3 months and then treated with acetylsalicylic acid for the subsequent two months. We then analyzed the metabolic and inflammatory status of their adipose and liver tissue by histological, molecular and biochemical analysis. KEY FINDINGS: Although ASA did not exert any effect on body weight, quantification of adipocyte size revealed that the drug slightly reduced adipocyte hypertrophy, however not sufficient so as to induce weight loss. Most importantly, ASA was able to improve insulin resistance. Gene expression profiles of pro- and anti-inflammatory cytokines as well as the expression of macrophage and lymphocyte markers revealed that HFD led to a marked macrophage accumulation in the adipose tissue and an increase of several pro-inflammatory cytokines, a situation almost completely reverted after ASA administration. In addition, liver steatosis caused by HFD was completely abrogated by ASA treatment. SIGNIFICANCE: ASA can efficiently ameliorate pathological conditions usually associated with obesity by inhibiting the inflammatory process occurring in the adipose tissue.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina/fisiología , Obesidad/tratamiento farmacológico , Tejido Adiposo/metabolismo , Tejido Adiposo/patología , Animales , Antiinflamatorios no Esteroideos/farmacología , Aspirina/farmacología , Modelos Animales de Enfermedad , Femenino , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Inflamación/patología , Ratones , Ratones Endogámicos C57BL , Obesidad/metabolismo , Obesidad/patología , Resultado del Tratamiento
12.
Food Chem ; 341(Pt 1): 128148, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33038776

RESUMEN

The brown seaweed Undaria pinnatifida polysaccharides show various biological activities, but their hypoglycemic activity and the underlying mechanism remain unclear. Here, three fractions of sulfated polysaccharides Up-3, Up-4, and Up-5 were prepared by microwave-assisted extraction from U. pinnatifida. In vitro assays demonstrated that Up-3 and Up-4 had strong α-glucosidase inhibitory activity, and Up-3, Up-4, and Up-5 could improve the glucose uptake in insulin-resistant HepG2 cells without affecting their viability. In vivo studies indicated Up-3 and Up-4 markedly reduced postprandial blood glucose levels. Up-U (a mixture of Up-3, Up-4, and Up-5), reduced fasting blood glucose levels, increased glucose tolerance and alleviated insulin resistance in HFD/STZ-induced hyperglycemic mice. Histopathological observation and hepatic glycogen measurement showed that Up-U alleviated the damage of the pancreas islet cell, reduced hepatic steatosis, and promoted hepatic glycogen synthesis. These findings suggest that Up-U could alleviate postprandial and HFD/STZ-induced hyperglycemia and was a potential agent for diabetes treatment.


Asunto(s)
Hipoglucemiantes/farmacología , Polisacáridos/farmacología , Algas Marinas/química , Undaria/química , Animales , Fraccionamiento Químico , Dieta Alta en Grasa/efectos adversos , Glucosa/metabolismo , Glucosa/farmacocinética , Células Hep G2 , Humanos , Hiperglucemia/tratamiento farmacológico , Hiperglucemia/etiología , Hipoglucemiantes/química , Insulina/farmacología , Resistencia a la Insulina , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Microondas , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Periodo Posprandial , Sulfatos/química
13.
Diving Hyperb Med ; 50(4): 386-390, 2020 Dec 20.
Artículo en Inglés | MEDLINE | ID: mdl-33325020

RESUMEN

INTRODUCTION: We have previously shown that hyperbaric oxygen treatment (HBOT) increased insulin sensitivity in men who were obese or overweight, both with and without type 2 diabetes. The aim of this study was to test whether this insulin-sensitising effect is seen in hyperbaric air (HA). METHODS: Men with type 2 diabetes who were obese or overweight were randomised to two groups: HBOT (n = 13) or HA (n = 11). A hyperinsulinaemic euglycaemic glucose clamp (80 mU·m-2·min-1) was performed at baseline and during hyperbaric intervention. Both groups were compressed to 203 kPa (two atmospheres absolute) for 90 minutes followed by a linear 30-minute decompression. The HBOT group breathed oxygen via a hood while the HA group breathed chamber air. Insulin sensitivity was assessed from the glucose infusion rate (GIR) during the last 30 minutes in the hyperbaric chamber (SS1) and the first 30 minutes after exit (SS2). Data were analysed for within-group effect by paired student t-test and between-group effect by one-way ANOVA. RESULTS: HBOT increased GIR by a mean 26% at SS1 (P = 0.04) and 23% at SS2 (P = 0.018). There was no significant change in GIR during or after HA. A between-group effect was evident for the change in GIR at SS1 in HBOT vs HA (P = 0.036). CONCLUSIONS: The pathway by which insulin sensitivity is increased in men with type 2 diabetes requires the high oxygen partial pressures of HBOT and should be further investigated. Insulin sensitivity was not changed in hyperbaric air.


Asunto(s)
Diabetes Mellitus Tipo 2 , Oxigenación Hiperbárica , Resistencia a la Insulina , Diabetes Mellitus Tipo 2/terapia , Humanos , Insulina , Masculino , Oxígeno
14.
PLoS One ; 15(12): e0241813, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33270666

RESUMEN

INTRODUCTION: The prevalence of obesity-related disorders has been steadily increasing over the past couple of decades. Diseases that were once only detected in adults are now prevalent in children, such as hyperlipidemia. The adipose tissue-derived hormonal factor C1q TNF Related Protein 3 (CTRP3) has been linked to triglyceride regulation especially in animal models. However, the relationship between circulating CTRP3 levels and obesity-related disorders in human subjects is controversial. CTRP3 can circulate in different oligomeric complexes: trimeric (<100 kDa), middle molecular weight (100-300 kDa), and high molecular weight (HMW) oligomeric complexes (>300 kDa). Previous work has identified that it is not the total amount of CTRP3 present in the serum, but the specific circulating oligomeric complexes that appear to be indicative of the relationship between CTRP3 and serum lipids levels. However, this work has not been examined in children. Therefore, the purpose of this study was to compare the levels of different oligomeric complexes of CTRP3 and circulating lipid levels among young children (aged 7-10 years). METHODS: Morphometric data and serum samples were collected and analyzed from a cross-sectional population of 62 children of self-identified Hispanic origin from a community health center, between 2015 and 2016. Serum analysis included adiponectin, insulin, leptin, ghrelin, glucagon, C-reactive peptide, triglyceride, cholesterol, IL-6, TNF, and CTRP3. Correlation analyses were conducted to explore the relationships between CTRP3 and other biomarkers. RESULTS: Total CTRP3 concentrations were significantly positively correlated with total cholesterol and HDL cholesterol. Whereas, HMW CTRP3 was not significantly associated with any variable measured. Conversely, the middle molecular weight (MMW) CTRP3 was negatively correlated with triglycerides levels, and very low-density lipoprotein (VLDL), insulin, and body mass index (BMI). The negative correlations between MMW CTRP3 and triglycerides and VLDLs were particularly strong (r2 = -0.826 and -0.827, respectively). CONCLUSION: Overall, these data indicate that the circulating oligomeric state of CTRP3 and not just total CTRP3 level is important for understanding the association between CTRP3 and metabolic diseases. Further, this work indicates that MMW CTRP3 plays an important role in triglyceride and VLDL regulation which requires further study.


Asunto(s)
Biomarcadores/sangre , Obesidad/sangre , Triglicéridos/sangre , Factores de Necrosis Tumoral/sangre , Adiponectina/sangre , Índice de Masa Corporal , Niño , Femenino , Humanos , Insulina/sangre , Resistencia a la Insulina/genética , Leptina/sangre , Masculino , Obesidad/epidemiología , Obesidad/genética , Obesidad/patología
15.
PLoS One ; 15(12): e0242332, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33270683

RESUMEN

We have reported previously that renal hemodynamic abnormalities exist in the prediabetic stage of type II diabetic rats. At this prediabetic stage these rats have hyperinsulinemia, insulin resistance and metabolic syndrome. It is well known that insulin resistance is frequently associated with renal abnormalities, but the mechanism underlying this association has remained speculative. Although insulin is known to modify renal hemodynamics, little is known about the roles of insulin receptor substrates (IRS1, IRS2) in the renal actions of insulin. To address this issue, the effects of insulin on renal function and renal hemodynamics were investigated in C57BL/6 (WT: wild type), insulin receptor substrate 1- knockout (IRS1-/-), and IRS2-knockout (IRS2-/-) mice. IRS2-/-mice had elevated glucose level as expected. 24-h urine collections and serum creatinine revealed that creatinine clearance did not significantly differ between these groups. Albuminuria was found in IRS1-/-and IRS2-/-groups. We examined the effects on the IRS during the administration of Losartan, which is widely used for diabetic nephropathy. After the administration of Losartan the IRS displayed improved renal hemodynamics. Moreover, the subjects were also given Pioglitazone, which improves insulin resistance. Losartan significantly reduced albuminuria in both groups. Pioglitazone also showed similar results. We assessed the autoregulatory responses of the total renal blood flow (RBF), the superficial (SBF) and the deep renal cortical blood flow (DBF) with stepwise reductions of renal perfusion pressure (RPP), which was induced by a manual clamp on the abdominal aorta. During the clamp induced reductions of the RPP by 10 to 20mm HG, RBF, SBF and the DBF fell significantly more in the IRS1 and IRS2 than in the WT mice. Furthermore micropuncture studies showded that compared to the WT tubuloglomerular feedback (TGF) responses of the stop flow pressure (Psf) were reduced in both the IRS1 -/- and IRS2 -/-. The results of the IRS1 and IRS2 mice displayed the pressence of hemodynamic abnormalities. Losartan and Pioglitazone have shown the potential to improve these abnormalities. In conclusion the results indicate that IRS plays a major role in the stimulation of renal functions and renal hemodynamics in type type II diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Nefropatías Diabéticas/genética , Hiperinsulinismo/genética , Proteínas Sustrato del Receptor de Insulina/genética , Albuminuria/sangre , Albuminuria/genética , Animales , Glucemia/genética , Creatinina/sangre , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/patología , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/patología , Monitorización Hemodinámica/métodos , Hemodinámica , Hiperinsulinismo/sangre , Hiperinsulinismo/patología , Insulina/sangre , Resistencia a la Insulina/genética , Riñón/irrigación sanguínea , Riñón/metabolismo , Riñón/patología , Masculino , Ratones , Ratones Noqueados , Estado Prediabético/sangre , Estado Prediabético/genética , Estado Prediabético/patología , Ratas , Circulación Renal/genética , Transducción de Señal/genética
16.
Ter Arkh ; 92(10): 15-22, 2020 Nov 24.
Artículo en Ruso | MEDLINE | ID: mdl-33346474

RESUMEN

AIM: Obese patients without diabetes present an interesting phenotype to explore protective mechanisms against type 2 diabetes (T2D) development. In our study we looked for specific hormonal features of obese patients without T2D. MATERIALS AND METHODS: We included 6 groups of patients with different metabolic profiles (n=212): controls with BMI25 kg/m2, HbA1c6%, age 30 years; patients with 25BMI30 kg/m2and HbA1c6%; patients with 25BMI30 kg/m2and HbA1c6%; patients with BMI30 kg/m2and HbA1c6% (+ Obesity - T2D) obese patients without T2D or prediabetes; patients with BMI30 kg/m2and newly-diagnosed T2D/prediabetes, HbA1c6%; patients with known history of T2D on glucose-lowering drugs with BMI30 kg/m2. Insulin, GLP-1, GIP were measured during glucose-tolerance test at 0, 30 and 120 minutes; insulin resistance (IR) was assessed by HOMA-IR. RESULTS: Waist circumference was bigger in patients with obesity despite their metabolic profile comparing to patients without obesity (p0.001). Waist-to-hip ratio was similar in patients with different metabolic status. According to IR + Obesity - T2D group had intermediate position: IR was higher in that group comparing to people without obesity, but was less that in patients with obesity and HbA1c6% (p0.001). + Obesity - T2D group had the most potent baseline insulin secretion, assessed by НОМА-%band the highest postprandial secretion, measured by insulinogenic index among all patient groups with obesity (p0.001). There was no significant difference in GLP-1 secretion; GIP secretion was higher in patients with BMI30 kg/m2comparing to people with BMI30 kg/m2(p0.01).


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Glucemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Péptido 1 Similar al Glucagón , Humanos , Insulina , Obesidad/complicaciones , Obesidad/epidemiología
18.
Med Hypotheses ; 144: 110231, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33254538

RESUMEN

The coronavirus disease 2019 (COVID-19) pandemic has increased exponentially in numbers with more than 20 million people infected around the globe. It is clear that COVID-19 is not a simple viral pneumonia, but presents with unusual pathophysiological effects. Of special interest is that SARS-CoV-2 utilises the angiotensin-converting enzyme-2 (ACE2) for cell entry and therefore has a direct effect on the renin angiotensin system (RAS). The RAS is primarily responsible for blood pressure control via the classic pathway. Recently numerous other pathological processes have been described due to stimulation of this classic pathway. There is also a protective RAS pathway medicated by ACE2 which may be suppressed in COVID-19. This leads to overstimulation of the classic pathway with adverse cardiovascular and respiratory effects, hypercoagulation, endothelial dysfunction, inflammation and insulin resistance. We hypothesize that overreaction of the renin-angiotensin-aldosterone may account for the myriad of unusual biochemical and clinical abnormalities noted in patients infected with SARS-CoV-2.


Asunto(s)
/metabolismo , Regulación de la Expresión Génica , Inflamación/metabolismo , Sistema Renina-Angiotensina/fisiología , Anciano , Presión Sanguínea , /virología , Enfermedades Cardiovasculares/complicaciones , Enfermedad Crítica , Citocinas/metabolismo , Femenino , Humanos , Resistencia a la Insulina , Unidades de Cuidados Intensivos , Masculino , Modelos Teóricos , Obesidad/complicaciones , Pandemias , /virología , Trombofilia/complicaciones
19.
Med Hypotheses ; 144: 110247, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33254553

RESUMEN

Type-2 diabetes (T2D) is a major comorbidity of COVID-19, and poorly controlled diabetes is associated with high mortality rate, emphasizing the necessity to improve glycemic control. Angiotensin-converting enzyme 2 (ACE2) is the receptor responsible for SARS-CoV-2 access to human cells, and ACE2 expression is increased in patients with diabetes and hypertension treated with ACE-inhibitors or angiotensin II receptor blockers. We hypothesize that an upregulation of ACE2 due to its non-enzymatic glycation could be considered, as well as a change of the protein tertiary structure in terms of amino acid (mostly lysine) available to be glycated. In fact, in a single ACE2 molecule, 34 lysine residues are present in the extracellular portion, and at least one of these is co-involved in a fundamental hydrogen-bond interaction with the SARS-CoV-2 receptor binding domain (RBD). The worse outcome of COVID-19 in people with diabetes could be related to the non-enzymatic glycation that triggers the activity of ACE2. Moreover, DNA methylation of genes regulating islet beta-cell function, as well as in insulin resistance of peripheral tissues such as liver, muscle, and adipose tissue may be involved, as already demonstrated for cancer conditions. DNA methylation, besides being considered as a biomarker to predict the risk of obesity and T2D, has been suggested also as a target for dietary and pharmacological treatments. The present observations may suggest further interventions in order to improve the outcome of COVID-19 in people affected by diabetes.


Asunto(s)
/complicaciones , Complicaciones de la Diabetes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/metabolismo , Tejido Adiposo , Biomarcadores/metabolismo , Comorbilidad , Metilación de ADN , Diabetes Mellitus Tipo 2/inmunología , Glicosilación , Humanos , Inmunoglobulina G/química , Resistencia a la Insulina , Metilación , Estudios Multicéntricos como Asunto , Neoplasias/metabolismo , Dominios Proteicos , Sistema Renina-Angiotensina , Estudios Retrospectivos , Regulación hacia Arriba
20.
Adv Gerontol ; 33(3): 479-487, 2020.
Artículo en Ruso | MEDLINE | ID: mdl-33280332

RESUMEN

Metabolic syndrome is a complex of interrelated disorders of carbohydrate and fat metabolism, as well as mechanisms for regulating blood pressure and endothelial function, which are based on a decrease in tissue sensitivity to insulin. Therefore, the leading component, pathophysiological basis and uniting factor of most of the symptoms described in metabolic syndrome is the resistance of peripheral tissues to the action of insulin, which is closely correlated with most metabolic disorders. It should be emphasized that almost all components of metabolic syndrome are established risk factors for developing cardiovascular diseases. The likelihood of developing metabolic syndrome increases with age. The article discusses the possibility of presenting the metabolic syndrome as a gerontological problem.


Asunto(s)
Enfermedades Cardiovasculares , Resistencia a la Insulina , Síndrome Metabólico , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Humanos , Insulina/metabolismo , Metabolismo de los Lípidos , Síndrome Metabólico/diagnóstico , Síndrome Metabólico/epidemiología , Factores de Riesgo
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