Insulin Infusion During Normoglycemia Modulates Insulin Secretion According to Whole-Body Insulin Sensitivity

OBJECTIVE—Glucose is the major stimulus for insulin release. Time course and amount of insulin secreted after glycemic stimulus are different between type 2 diabetes mellitus (T2DM) patients and healthy subjects. In rodents, it was demonstrated that insulin can modulate its own release. Previous studies in humans yielded contrasting results: Insulin was shown to have an enhancing effect, no effect, or a suppressive effect on its own secretion. Thus, we aimed to evaluate short-term effects of human insulin infusion on insulin secretion during normoglycemia in healthy humans and T2DM subjects of both sex. RESEARCH DESIGN AND METHODS—Hyperinsulinemic-isoglycemic clamps with whole-body insulin-sensitivity (M) and C-peptide measurements for insulin secretion modeling were performed in 65 insulin-sensitive (IS) subjects (45 6 1 year, BMI: 24.8 6 0.5 kg/m2), 17 insulin-resistant (IR) subjects (466 2 years, 28.16 1.3 kg/m2), and 20 T2DMpatients (566 2 years, 28.0 6 0.8 kg/m2; HbA1c = 6.7 6 0.1%). RESULTS—IS subjects (M = 8.8 6 0.3 mg z min21 z kg21) had higher (P, 0.00001) whole-body insulin sensitivity than IR subjects (M = 4.0 6 0.2) and T2DM patients (M = 4.3 6 0.5). Insulin secretion profiles during clamp were different (P, 0.00001) among the groups, in

Holistic corpus-based dialectology

This paper is concerned with sketching future directions for corpus-based dialectology. We advocate a holistic approach to the study of geographically conditioned linguistic variability, and we present a suitable methodology, 'corpusbased dialectometry', in exactly this spirit. Specifically, we argue that in order to live up to the potential of the corpus-based method, practitioners need to (i) abandon their exclusive focus on individual linguistic features in favor of the study of feature aggregates, (ii) draw on computationally advanced multivariate analysis techniques (such as multidimensional scaling, cluster analysis, and principal component analysis), and (iii) aid interpretation of empirical results by marshalling state-of-the-art data visualization techniques. To exemplify this line of analysis, we present a case study which explores joint frequency variability of 57 morphosyntax features in 34 dialects all over Great Britain

Exercise in type 2 diabetes: to resist or to endure?

There is now evidence that a single bout of endurance (aerobic) or resistance exercise reduces 24 h post-exercise subcutaneous glucose profiles to the same extent in insulin-resistant humans with or without type 2 diabetes. However, it remains to be determined which group would benefit most from specific exercise protocols, particularly with regard to long-term glycaemic control. Acute aerobic exercise first accelerates translocation of myocellular glucose transporters via AMP-activated protein kinase, calcium release and mitogen-activated protein kinase, but also improves insulin-dependent glucose transport/phosphorylation via distal components of insulin signalling (phosphoinositide-dependent kinase 1, TBC1 domain family, members 1 and 4, Rac1, protein kinase C). Post-exercise effects involve peroxisome-proliferator activated receptor-γ coactivator 1α and lead to ATP synthesis, which may be modulated by variants in genes such as NDUFB6. While mechanisms of acute resistance-type exercise are less clear, chronic resistance training activates the mammalian target of rapamycin/serine kinase 6 pathway, ultimately increasing protein synthesis and muscle mass. Over the long term, adherence to rather than differences in metabolic variables between specific modes of regular exercise might ultimately determine their efficacy. Taken together, studies are now needed to address the variability of individual responses to long-term resistance and endurance training in real life

Liver Enzymes Are Associated With Hepatic Insulin Resistance, Insulin Secretion, and Glucagon Concentration in Healthy Men and Women

International audienceOBJECTIVE: The pathophysiological mechanisms to explain the association between risk of type 2 diabetes and elevated concentrations of γ-glutamyltransferase (GGT) and alanineaminotransferase (ALT) remain poorly characterized. We explored the association of liver enzymes with peripheral and hepatic insulin resistance, insulin secretion, insulin clearance, and glucagon concentration. RESEARCH DESIGN AND METHODS: We studied 1,309 nondiabetic individuals from the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study; all had a euglycemic-hyperinsulinemic clamp and an oral glucose tolerance test (OGTT) with assessment of insulin secretion and hepatic insulin extraction. The hepatic insulin resistance index was calculated in 393 individuals. RESULTS: In both men and women, plasma concentrations of GGT and ALT were inversely related with insulin sensitivity (M/I) (all P < 0.01). Likewise, the hepatic insulin resistance index was positively correlated with both GGT (r = 0.37, P < 0.0001, men; r = 0.36, P < 0.0001, women) and ALT (r = 0.25, P = 0.0005, men; r = 0.18, P = 0.01, women). These associations persisted in multivariable models. Increased GGT and ALT were significantly associated with higher insulin secretion rates and with both reduced endogenous clearance of insulin and hepatic insulin extraction during the OGTT (P = 0.0005 in men; P = 0.003 in women). Plasma fasting glucagon levels increased over ALT quartiles (men, quartile 4 vs. quartile 1 11.2 ± 5.1 vs. 9.3 ± 3.8 pmol/L, respectively, P = 0.0002; women, 9.0 ± 4.3 vs. 7.6 ± 3.1, P = 0.001). CONCLUSIONS: In healthy individuals, increased GGT and ALT were biomarkers of both systemic and hepatic insulin resistance with concomitant increased insulin secretion and decreased hepatic insulin clearance. The novel finding of a positive correlation between ALT and fasting glucagon level concentrations warrants confirmation in type 2 diabetes