The purpose of the present work was to have a closer view on the changes in the regulation of glycogen synthase (GS) activity by insulin in relationship with the impairment of nonoxidative glucose ...disposal in human obesity. Obese patients with normal glucose tolerance (12), impaired glucose tolerance (11), diabetes (10), and lean control subjects (15) participated to the study. A euglycemic, hyperinsulinemic clamp was performed and associated with indirect calorimetry. Muscle needle biopsies were taken before and at the end of the 2-hour clamp for measurements of glycogen synthase fractional velocity and total activity. Total GS activity was significantly decreased (
P lt .05), while its percent activation by insulin was still normal in the obese glucose-tolerant group, and nonoxidative glucose disposal was decreased by 56% (
P lt .001) and glucose oxidation still normal. Total GS activity was decreased by about 50% (
P lt .01) and GS was unresponsive to insulin in the glucose-intolerant and diabetic groups. In conclusion, our data show that insulin-stimulated nonoxidative glucose disposal and total glycogen synthase are very early defects observed in obese patients.
Au cours du siècle dernier, l’étude des différences individuelles en psychologie a pu être jugée comme secondaire et considérée comme de la « science mineure ». L’emprunt de méthodes en vigueur dans ...les sciences expérimentales se fixait pour objectif de mettre en évidence des lois générales, les différences entre individus étant perçues comme des variables parasites qu’il s’agissait de neutraliser car rendant trop complexes les phénomènes à analyser. Les nouveaux outils conceptuels et méthodologiques développés par les différentialistes permettent de traiter cette complexité. On assiste à une intégration croissante des différences individuelles dans les recherches sur la cognition, les émotions, le développement, du handicap, le vieillissement, les conduites sociales. De façon symétrique, les études de psychologie différentielle, prennent de plus en plus en compte la variabilité intra-individuelle. Ces recherches placent la psychologie différentielle à l’articulation d’autres disciplines. D’une rencontre biennale lors des « Journées de psychologie différentielle ». Les XIXe Journées organisées par l’université d’Aix-Marseille en 2010 ont été consacrées à l’inscription de l’étude des différences individuelles dans les différents champs de la psychologie et dans des sciences avec qui elle interagit fortement (neurosciences et génétique). Trois conférenciers de renommée internationale, Andreas Demetriou, Dorett Boomsma, et Robert Vallerand ont participé à ce débat. Les recherches présentées ici, adossées aux modèles et méthodes les plus récents, attestent de l’apport de cette discipline à tous les domaines de la psychologie et à ses applications.
The requisites for energy expenditure are covered mainly by two major substrates, glucose and free fatty acids (FFA). Their regulation and metabolism differ. After carbohydrate ingestion, glucose is ...rapidly oxidized or stored in muscles and liver. There is a constant alternance between glucose storage as glycogen after meals and glycogen mobilization in the postabsorptive state when plasma glucose has returned to the basal state. Impairment of this alternance, in particular when glycogen stores are not being used, may lead to glucose intolerance and insulin resistance. Ingestion of lipids is not followed by an immediate increase in lipid oxidation, but FFA are stored as triglycerides in different tissues. Lipolysis occurs in the fasting state from tissue triglycerides and favors lipid oxidation. Lipid oxidation is typically increased in obesity. The preferential use of FFA from triglyceride store for energy expenditure in obesity is responsible for the decrease in glucose mobilization from glycogen stores. This leads to a negative feedback of muscle and liver glycogen on glycogen synthase activity and consequently on glucose storage. It results in glucose intolerance after carbohydrate ingestion. Diabetes develops in obesity, usually after a long period of glucose intolerance, when glycemia does not return to the basal state. In obesity, glucose intolerance and insulin resistance can be prevented, or if already existing, can be decreased by stimulating glycogen mobilization by exercise, thermogenesis-stimulating drugs, and weight loss, which reduces fat stores and decreases lipid oxidation.
Glucose-induced thermogenesis (GIT) after a 100-g oral glucose load was measured by continuous indirect calorimetry in 32 nondiabetic and diabetic obese subjects and compared to 17 young and 13 ...middle aged control subjects. The obese subjects were divided into three groups: A (n = 12) normal glucose tolerance, B (n = 13) impaired glucose tolerance, and C (n = 7) diabetics, and were studied before and after a body weight loss ranging from 9.6 to 33.5 kg consecutive to a 4 to 6 months hypocaloric diet. GIT, measured over 3 h and expressed as percentage of the energy content of the load, was significantly reduced in obese groups A and C (6.2 ± 0.6, and 3.8 ± 0.7%, respectively) when compared to their age-matched control groups: 8.6 ± 0.7 (young) and 5.8 ± 0.3% (middle aged). Obese group B had a GIT of 6.1 ± 0.6% which was lower than that of the young control group but not different from the middle-aged control group. After weight loss, GIT in the obese was further reduced in groups A and B than before weight loss: ie, 3.4 ± 0.6 (p < 0.001), 3.7 ± 0.5 (p < 0.01) respectively, whereas in group C, weight loss induced no further diminution in GIT (3.8 ± 0.6%). These results support the concept of a thermogenic defect after glucose ingestion in obese individuals which is not the consequence of their excess body weight but may be one of the factors favoring the relapse of obesity after weight loss.
Fourteen overweight insulin-treated type 2 diabetic patients ate a breakfast, consisting of either muesli (slow release starch: SRS) or cornflakes (fast release starch: FRS), in either case with milk ...(46 g carbohydrate), during two consecutive randomized crossover periods of two weeks. The rest of the diet remained unchanged. At the end of each period the patients underwent a glucose tolerance test after an overnight fast without their usual evening insulin injection. Both mean plasma glucose responses curves were identical after the two dietary periods, but plasma insulin was significantly lower at zero (-17%, P less than 0.05) and 2 h (-21%, P less than 0.05) at the end of the muesli (SRS) period as compared to the cornflakes (FRS) period. The mean day-long plasma glucose level (four measurements) at the end of the muesli period was 21% (P = 0.023) lower than after the cornflakes period. These results show that switching, at breakfast only, from standard cereals to slow release starch cereals improves the carbohydrate metabolism of diabetic patients. In addition, the fact that diabetic patients could reduce their insulin requirement (P less than 0.05) with concomitant reduction of their daily blood glucose level implies that sensitivity to insulin was improved by slow release starct foods consumed at breakfast.
The effect of skim milk from cows immunized against a variety of human intestinal bacteria on serum cholesterol concentrations was examined in 11 patients with primary hypercholesterolemia in a ...24-wk, randomized, double-blind, placebo-controlled, crossover study. After a 4-wk baseline period, patients were treated for 8 wk either with skim milk from immunized cows (active) or with control skim milk (placebo) followed by an 8-wk period with the treatment order reversed. Eight weeks of active treatment with skim milk from immunized cows reduced serum total cholesterol concentrations by 0.52 +/- 0.59 mmol/L (average +/- SD; P 0.025), or 8%, LDL cholesterol by 0.16 +/- 0.59 mmol/L (NS), or 4%, and the atherogenic index (total cholesterol/HDL cholesterol) by 0.42 +/- 1.85 (P 0.05), or 8%, compared with the placebo treatment. Reversal of the favorable development occurred upon cessation of active treatment. We conclude that daily supplementation of a normal diet with skim milk from immunized cows can result in a significant reduction of elevated blood cholesterol concentrations
