Type 2 diabetes is a complex disorder with diminished insulin secretion and insulin action contributing to the hyperglycemia and wide range of metabolic defects that underlie the disease. The contribution of glucose metabolic pathways per se in the pathogenesis of the disease remains unclear. The cellular fate of glucose begins with glucose transport and phosphorylation. Subsequent pathways of glucose utilization include aerobic and anaerobic glycolysis, glycogen formation, and conversion to other intermediates in the hexose phosphate or hexosamine biosynthesis pathways. Abnormalities in each pathway may occur in diabetic subjects; however, it is unclear whether perturbations in these may lead to diabetes or are a consequence of the multiple metabolic abnormalities found in the disease. This review is focused on the cellular fate of glucose and relevance to human type 2 diabetes. (Endocrine Reviews 25: 2004)

OBJECTIVE -To evaluate whether a 5-week low-glycemic index (LGI) diet versus a highglycemic index (HGI) diet can modify glucose and lipid metabolism as well as total fat mass in nondiabetic men.RESEARCH DESIGN AND METHODS -In this study, 11 healthy men were randomly allocated to 5 weeks of an LGI or HGI diet separated by a 5-week washout interval in a crossover design. RESULTS -TheLGI diet resulted in lower postprandial plasma glucose and insulin profiles and areas under the curve (AUCs) than the HGI diet. A 5-week period of the LGI diet lowered plasma triacylglycerol excursion after lunch (AUC, P Ͻ 0.05 LGI vs. HGI). These modifications were associated with a decrease in the total fat mass by ϳ700 g (P Ͻ 0.05) and a tendency to increase lean body mass (P Ͻ 0.07) without any change in body weight. This decrease in fat mass was accompanied by a decrease in leptin, lipoprotein lipase, and hormone-sensitive lipase RNAm quantities in the subcutaneous abdominal adipose tissue (P Ͻ 0.05).CONCLUSIONS -We concluded that 5 weeks of an LGI diet ameliorates some plasma lipid parameters, decreases total fat mass, and tends to increase lean body mass without changing body weight. These changes were accompanied by a decrease in the expression of some genes implicated in lipid metabolism. Such a diet could be of benefit to healthy, slightly overweight subjects and might play a role in the prevention of metabolic diseases and their cardiovascular complications. Diabetes Care 25:822-828, 2002T he insulin-resistance syndrome is a major risk factor for abnormal carbohydrate metabolism and atherosclerotic and coronary heart diseases (1). Recent prospective studies have incriminated the high-glycemic index (HGI) diet in the genesis of insulin resistance and type 2 diabetes (2). High postprandial plasma glucose and insulin excursions are assumed by some authors (3) to be independent predictors of risk for atherosclerotic diseases. Epidemiological evidence shows that the relationship between plasma glucose concentrations and cardiovascular diseases extends well below the glucose level defined for diabetes and even for impaired glucose tolerance. Therefore, interventions to reduce postprandial glycemia in the normal population could reduce the risk of developing atherosclerotic heart disease and/or diabetes. Dietary intervention might be one of the major approaches in diabetic patients' care, but it might even be useful in normal nondiabetic individuals.In diabetic subjects, the chronic consumption of a low-glycemic index (LGI) diet is generally found to improve plasma glucose and lipid profiles (4). In clinical practice, however, the chronic use of LGI foods is still questioned (5).In nondiabetic subjects, few data exist on the effects of short-and long-term consumption of LGI foods (6 -8). Behall et al. (6) demonstrated that an LGI diet resulted in a decrease in both glycemic area under the curve (AUC) and plasma cholesterol and triacylglycerol levels. Most of these studies, with one exception (8), have demonstrated beneficial effe...

Islet β-cells express both insulin receptors and insulin-signaling proteins. Recent evidence from rodents in vivo and from islets isolated from rodents or humans suggests that the insulin signaling pathway is physiologically important for glucose sensing. We evaluated whether insulin regulates β-cell function in healthy humans in vivo. Glucose-induced insulin secretion was assessed in healthy humans following 4-h saline (low insulin/sham clamp) or isoglycemic-hyperinsulinemic (high insulin) clamps using B28-Asp insulin that could be immunologically distinguished from endogenous insulin. Insulin and C-peptide clearance were evaluated to understand the impact of hyperinsulinemia on estimates of β-cell function. Preexposure to exogenous insulin increased the endogenous insulin secretory response to glucose by ≈40%. C-peptide response also increased, although not to the level predicted by insulin. Insulin clearance was not saturated at hyperinsulinemia, but metabolic clearance of C-peptide, assessed by infusion of stable isotope-labeled C-peptide, increased modestly during hyperinsulinemic clamp. These studies demonstrate that insulin potentiates glucose-stimulated insulin secretion in vivo in healthy humans. In addition, hyperinsulinemia increases C-peptide clearance, which may lead to modest underestimation of β-cell secretory response when using these methods during prolonged dynamic testing. beta cell | type 2 diabetes mellitus | insulin resistance | insulin clearance |