The effect of acute exercise on glycogen synthesis rate in obese subjects studied by 13C MRS

In obesity, insulin-stimulated glucose uptake in skeletal muscle is decreased. We investigated whether the stimulatory effect of acute exercise on glucose uptake and subsequent glycogen synthesis was normal. The study was performed on 18 healthy volunteers, 9 obese (BMI = 32.6 ± 1.2 kg/m2, mean ± SEM) and 9 lean (BMI = 22.0 ± 0.9 kg/m2), matched for age and gender. All participants underwent a euglycemic hyperinsulinemic clamp, showing reduced glucose uptake in the obese group (P = 0.01), during which they performed a short intense local exercise (single-legged toe lifting). Dynamic glucose incorporation into glycogen in the gastrocnemius muscle before and after exercise was assessed by 13C magnetic resonance spectroscopy combined with infusion of [1-13C]glucose. Blood flow was measured to investigate its potential contribution to glucose uptake. Before exercise, glycogen synthesis rate tended to be lower in obese subjects compared with lean (78 ± 14 vs. 132 ± 24 μmol/kg muscle/min; P = 0.07). Exercise induced highly significant rises in glycogen synthesis rates in both groups, but the increase in obese subjects was reduced compared with lean (112 ± 15 vs. 186 ± 27 μmol/kg muscle/min; P = 0.03), although the relative increase was similar (184 ± 35 vs. 202 ± 51%; P = 0.78). After exercise, blood flow increased equally in both groups, without a temporal relationship with the rate of glycogen synthesis. In conclusion, this study shows a stimulatory effect of a short bout of acute exercise on insulin-induced glycogen synthesis rate that is reduced in absolute values but similar in percentages in obese subjects. These results suggest a shared pathway between insulin- and exercise-induced glucose uptake and subsequent glycogen synthesis

Reappraisal of Metformin Efficacy in the Treatment of Type 2 Diabetes: A Meta-Analysis of Randomised Controlled Trials

Catherine Cornu and colleagues performed a meta-analysis of randomised controlled trials of metformin efficacy on cardiovascular morbidity or mortality in patients with type 2 diabetes and showed that although metformin is considered the gold standard, its benefit/risk ratio remains uncertain

Socioeconomic variation in child educational and socioeconomic attainment after parental death in Sweden

In this study we use Swedish population register data to examine whether parental death differentially affects educational and occupational attainment according to the socioeconomic status of the parent who dies, and the socioeconomic status of the surviving parent and extended kin. That is, we examine whether parental death has an equalizing or exacerbating effect on offspring socioeconomic attainment, and also whether the socioeconomic status of the rest of the family plays a meaningful role in compensating for parental death. Using data on cohorts born 1973 to 1982 we examine five different outcomes, which are grade point average (GPA) at age 16 in high school, the transition from lower to upper-secondary education, the transition to tertiary education, overall educational attainment, and occupational status by age 30. We match families based upon antemortem parental socioeconomic trajectories. Overall we find mixed results in our between-family regression analyses adjusting for observables, with inconsistent evidence suggesting that losing a parent with very high socioeconomic resources is worse, and some evidence for a protective effect if the socioeconomic resources of the surviving parent and extended family members are at the top of the distribution. Using sibling fixed effects models that adjust for unobservable factors shared within the family, we see zero results for moderation by parents’ SES, but find consistent evidence that it is worse to lose a father at a younger age if grandparents have higher ranked occupations. We discuss possible interpretations of our findings

Decreased Thioredoxin-1 and Increased HSP90 Expression in Skeletal Muscle in Subjects with Type 2 Diabetes or Impaired Glucose Tolerance

In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) ( = 10) were compared with subjects with impaired glucose tolerance (IGT) ( = 8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower ( = 0.031) and HSP90 was 380% higher ( < 0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research

Metformin treatment significantly enhances intestinal glucose uptake in patients with type 2 diabetes: Results from a randomized clinical trial

AimsMetformin therapy is associated with diffuse intestinal 18F-fluoro-deoxyglucose (FDG) accumulation in clinical diagnostics using routine FDG-PET imaging. We aimed to study whether metformin induced glucose uptake in intestine is associated with the improved glycaemic control in patients with type 2 diabetes. Therefore, we compared the effects of metformin and rosiglitazone on intestinal glucose metabolism in patients with type 2 diabetes in a randomized placebo controlled clinical trial, and further, to understand the underlying mechanism, evaluated the effect of metformin in rats.MethodsForty-one patients with newly diagnosed type 2 diabetes were randomized to metformin (1 g, b.i.d), rosiglitazone (4 mg, b.i.d), or placebo in a 26-week double-blind trial. Tissue specific intestinal glucose uptake was measured before and after the treatment period using FDG-PET during euglycemic hyperinsulinemia. In addition, rats were treated with metformin or vehicle for 12 weeks, and intestinal FDG uptake was measured in vivo and with autoradiography.ResultsGlucose uptake increased 2-fold in the small intestine and 3-fold in the colon for the metformin group and associated with improved glycemic control. Rosiglitazone increased only slightly intestinal glucose uptake. In rodents, metformin treatment enhanced intestinal FDG retention (P = 0.002), which was localized in the mucosal enterocytes of the small intestine.ConclusionsMetformin treatment significantly enhances intestinal glucose uptake from the circulation of patients with type 2 diabetes. This intestine-specific effect is associated with improved glycemic control and localized to mucosal layer. These human findings demonstrate directs effect of metformin on intestinal metabolism and elucidate the actions of metformin.</div