1,721,095 research outputs found
Effects of weight loss and calorie restriction on carbohydrate metabolism
No full textThis article provides an overview of the most recent molecular and clinical outcomes of studies that investigate the effect of weight loss and calorie restriction on carbohydrate metabolism, obtained either by dieting or bariatric surgery. It will focus on aspects of carbohydrate metabolism related to insulin action. The discussion begins by describing attempts to restrain calories by shifting the macronutrient balance from carbohydrates to a higher protein and fat content. The topics covered include insulin secretion and resistance, glucose homeostasis and allostasis, changes in the secretive patterns of adipose tissue and the entero-insular axis
Effects of dietary fatty acids on insulin sensitivity and secretion
No full textGlobalization and global market have contributed to increased consumption of high-fat, energy-dense diets, particularly rich in saturated fatty acids( SFAs). Polyunsaturated fatty acids (PUFAs) regulate fuel partitioning within the cells by inducing their own oxidation through the reduction of lipogenic gene expression and the enhancement of the expression of those genes controlling lipid oxidation and thermogenesis. Moreover, PUFAs prevent insulin resistance by increasing membrane fluidity and GLUT4 transport. In contrast, SFAs are stored in non-adipocyte cells as triglycerides (TG) leading to cellular damage as a sequence of their lipotoxicity. Triglyceride accumulation in skeletal muscle cells (IMTG) derives from increased FA uptake coupled with deficient FA oxidation. High levels of circulating FAs enhance the expression of FA translocase the FA transport proteins within the myocites. The biochemical mechanisms responsible for lower fatty acid oxidation involve reduced carnitine palmitoyl transferase (CPT) activity, as a likely consequence of increased intracellular concentrations of malonyl-CoA; reduced glycogen synthase activity; and impairment of insulin signalling and glucose transport. The depletion of IMTG depots is strictly associated with an improvement of insulin sensitivity, via a reduced acetyl-CoA carboxylase (ACC) mRNA expression and an increased GLUT4 expression and pyruvate dehydrogenase (PDH) activity. In pancreatic islets, TG accumulation causes impairment of insulin secretion. In rat models, beta-cell dysfunction is related to increased triacylglycerol content in islets, increased production of nitric oxide, ceramide synthesis and beta-cell apoptosis. The decreased insulin gene promoter activity and binding of the pancreas-duodenum homeobox-1 (PDX-1) transcription factor to the insulin gene seem to mediate TG effect in islets. In humans, acute and prolonged effects of FAs on glucose-stimulated insulin secretion have been widely investigated as well as the effect of high-fat diets on insulin sensitivity and secretion and on the development of type 2 diabetes
Beta-cell function in severely obese type 2 diabetic patients: long-term effects of bariatric surgery
No full textShape of the OGTT glucose curve and risk of impaired glucose metabolism in the EGIR-RISC cohort
No full textObjective To study whether the shape of the oral glucose tolerance test (OGTT)-glucose curve is a stable trait over time; it is associated with differences in insulin sensitivity, ß-cell function and risk of impaired fasting glucose (IFG) and glucose tolerance (IGT) in the Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort. Methods OGTT-glucose curve shape was classified as monophasic, biphasic, triphasic and anomalous in 915 individuals. Oral glucose insulin sensitivity (OGIS), Matsuda insulin sensitivity index (ISI) and ß-cell function were assessed at baseline and 3 years apart. Results The OGTT-glucose curve had the same baseline shape after 3 years in 540 people (59%; κ = 0.115; p < 0.0001). Seventy percent of the participants presented with monophasic OGTT-glucose curve shape at baseline and after 3 years (percent positive agreement 0.74). Baseline monophasic shape was associated with significant increased risk of IFG (OR 1.514; 95% CI 1.084–2.116; p = 0.015); biphasic shape with reduced risk of IGT (OR 0.539; 95% CI 0.310–0.936) and triphasic shape with reduced risk of IFG (OR 0.493; 95% CI 0.228–1.066; P = 0.043) after 3 years. Increased risks of IFG (OR 1.509; 95% CI 1.008–2.260; p = 0.05) and IGT (OR 1.947; 95% CI 1.085–3.494; p = 0.02) were found in people who kept stable monophasic morphology over time and in switchers from biphasic to monophasic shape (OR of IGT = 3.085; 95% CI 1.377–6.912; p = 0.001). Conclusion After 3 years follow-up, the OGTT-glucose shape was stable in 59% of the RISC cohort. Shapes were associated with different OGIS and ß-cell function; persistence over time of the monophasic shape and switch from biphasic to monophasic shape with increased risk of impaired glucose metabolism
Nonalcoholic fatty liver disease in children
No full textIn view of the epidemic obesity in childhood, facing the disease and its associated morbidities early at this age becomes crucial for public health researchers and care givers. The present review focuses on pediatric Non Alcoholic Fatty Liver Disease (NAFLD) among co-morbidities, being the disease yet under diagnosed and under treated despite a prevalence growing exponentially. Evidences suggest that the environmental background for the development of NAFLD may be established in early life, and that the duration of the disease affects probably the likelihood of progression to more severe disease (necro-inflammation or Non Alcoholic SteatoHepatitis, also termed, NASH; fibrosis and cirrhosis). NAFLD associates with abdominal obesity, insulin resistance and features of metabolic syndrome. In genetically prone individuals, malnutrition (i.e., excessive consumption of saturated fats and refined sugars) leads to the derangement of the adipose tissue architecture and homeostasis, the peripheral and hepatic resistance to insulin-stimulated glucose uptake, thus favoring a condition of chronic low-grade inflammation. Excessive nutrients cannot be stored in the adipose tissue and overflow elsewhere, mainly to the muscle tissue and liver. Fat deposition in both sites enhances insulin resistance and further deposition of fats in a vicious manner. What is of special interest comparing NAFLD in children and adults is that the histological appearance of the disease differs significantly, likely representing a yet physiological response to environmental stressors in children and a long-term adaptation in adults. In this article, we review the current concepts about paediatric NAFLD, its pathogenesis, diagnosis and treatment, with particular regard to lifestyle and foods habits
Twenty-four hour energy expenditure and skeletal muscle gene expression changes after bariatric surgery
No full textObesity is characterized by decreased insulin-stimulated glucose uptake in muscle and shift from glucose to lipid oxidation, the so-called metabolic inflexibility. Biliopancreatic diversion (BPD), a mainly malabsorptive bariatric operation, determines a prompt improvement of insulin resistance, but the mechanisms are still unclear
Metabolic endotoxemia and saturated fat contribute to circulating NGAL concentrations in subjects with insulin resistance
No full textLipocalin-2 (neutrophil gelatinase-associated lipocalin, NGAL) is an innate immune system protein that has been linked to insulin resistance and obesity, but the mechanisms behind these associations are poorly known. We hypothesized that endotoxin (lipopolysaccharide, LPS) and fat intake were in the background of these associations.Design:We studied four cohorts: (1) a cross-sectional study in 194 subjects; (2) the changes in NGAL concentration induced by diet and weight loss in 36 obese women (with circadian rhythm in 8 of them); (3) the effects of acute fat intake on circulating NGAL concentration in 42 morbidly obese subjects; and (4) LPS-induced NGAL secretion ex vivo (whole blood and adipose tissue explants)
NEFA-glucose comodulation model of beta-cell insulin secretion in 24-h multiple-meal test
No full textThere is experimental evidence that a source of fatty acids (FAs) that is either exogenous or endogenous is necessary to support normal insulin secretion. Therefore, FAs comodulate the glucose-induced pancreatic insulin secretion. To assess the role of FAs, 16 morbidly obese nondiabetic patients and 6 healthy volunteers were studied. The controls and the obese subjects, before and after diet-induced weight loss, spent 24 h in a calorimetric chamber, where they consumed standardized meals. Hourly blood samples were drawn from a central venous catheter for the measurement of glucose, C-peptide, and nonesterified fatty acid (NEFA) concentrations. Insulin sensitivity was measured (as the M value) by euglycemic hyperinsulinemic clamp. In the present study, we propose a mathematical model in which insulin secretion rate (ISR) is expressed as a function of both plasma glucose and NEFA concentrations. Model parameters, obtained by fitting the individual experimental data of plasma C-peptide concentration, gave an estimated ISR comparable with that obtained by the deconvolution method. To evaluate the performance of the model in an experimental condition in which incretin effect was minimized, previous data on insulin secretion following a butter load and subsequent hyperglycemic clamp were reanalyzed. This model of nutrient-stimulated insulin secretion is the first attempt to represent in a simple way the interaction between glucose and NEFA in the regulation of insulin secretion in the beta-cell and explains, at least in part, the "potentiation factor" used in previous models to account for other control factors different from glucose after either an intravenous infusion of glucose or a mixed meal
Mechanisms of hyperinsulinaemia in Child's disease grade B liver cirrhosis investigated in free living conditions.
No full text- …
