Repeated prolonged whole-body low-intensity exercise: effects on insulin sensitivity and limb muscle adaptations.

This study investigates the effect of prolonged whole-body low-intensity exercise on insulin sensitivity and the limb muscle adaptive response. Seven male subjects (weight, 90.2 +/- 3.2 kg; age, 35 +/- 3 years) completed a 32-day unsupported crossing of the Greenland icecap on cross-country skies pulling sleighs. The subjects were studied before and 3 to 4 days after the crossing of the icecap. Subjects came in overnight fasted, and an intravenous glucose tolerance test (IVGTT) was done. A biopsy was obtained from the vastus lateralis and deltoid muscle. On a separate day, a progressive test was performed to establish maximal oxygen uptake. During the crossing, subjects skied for 342 +/- 41 min/d. Peak oxygen uptake (4.6 +/- 0.2 L/min) was decreased (P < .05) by 7% after the crossing and body mass decreased (P < .05) by 7.1 +/- 0.2 kg, of which 4.4 +/- 0.5 kg was fat mass and 2.7 +/- 0.2 kg lean body mass. Glycosylated hemoglobin (5.6% +/- 0.01%) was not affected by the crossing. The IVGTT data revealed that insulin sensitivity (7.3 +/- 0.6 mU x L-1 x min-1) and glucose effectiveness (0.024 +/- 0.002 min-1) were not changed after the crossing. Similarly, the IVGTT data, when expressed per kilogram of lean body mass or body mass, were not affected by the crossing. Citrate synthase activity was higher (P < .05) in the leg (29 +/- 1 micromol x g-1 x min-1) than in the arm muscle (16 +/- 2 micromol x g-1 x min-1) and was unchanged after the crossing. Muscle GLUT4 protein concentration was higher (P < .05) in the leg (104 +/- 10 arbitrary units) than in the arm (54 +/- 9 arbitrary units) and was not changed in the leg, but was increased (P < .05) by 70% to 91 +/- 9 arbitrary units in the arm after the crossing. In conclusion, the increased glucose transporter expression in arm muscle may compensate for the loss of lean body mass and the decrease in aerobic fitness and thereby contribute to the maintenance of whole-body insulin sensitivity after prolonged low-intensity exercise training.

Stevioside does not cause increased basal insulin secretion or beta-cell desensitization as does the sulphonylurea, glibenclamide: studies in vitro.

We have shown that stevioside (SVS) enhances insulin secretion and thus may have a potential role as antihyperglycemic agent in the treatment of type 2 diabetes mellitus. However, whether SVS stimulates basal insulin secretion (BIS) and/or cause desensitization of beta cells like sulphonylureas (SU), e.g. glibenclamide (GB), is not known. To explore and compare the effects of SVS pretreatment with those of GB and glucagon-like peptide-1 (GLP-1), we exposed isolated mouse islets to low or high glucose for 1 h after short-term (2 h) or long-term (24 h) pretreatment with SVS, GB or GLP-1, respectively. BIS at 3.3 or 5.5 mM glucose were not changed after short-term pretreatment with SVS (10(-7) M), while it increased about three folds after pretreatment with GB (10(-7) M). Glucose stimulated insulin secretion (GSIS) (16.7 mM) increased dose-dependently after long-term pretreatment with SVS at concentrations from 10(-7) to 10(-5) M. Pretreatment for 24 h with GB (10(-7) M) increased the subsequent BIS (3.3 mM glucose) (p < 0.001), but decreased GSIS (16.7 mM glucose) (p < 0.001). In contrast SVS (10(-7) M) and GLP-1 (10(-7) M) did not stimulate BIS but both enhanced the subsequent GSIS (16.7 mM glucose) (p < 0.05 and p < 0.05, respectively). While SVS pretreatment increased the intracellular insulin content, GB pretreatment decreased the insulin content. Our study suggests that SVS pretreatment does not cause a stimulation of BIS and does not desensitize beta-cells, i.e. SVS seems to have advantageous characteristics to GB as a potential treatment of type 2 diabetes.

The short-term effect of fatty acids on glucagon secretion is influenced by their chain length, spatial configuration, and degree of unsaturation: studies in vitro.

The influence of fatty acids on beta cell function has been well established whereas little is known about the role of fatty acids on alpha cell function. The aim of our study was to investigate the short-term effects of chain length, spatial configuration, and degree of unsaturation of fatty acids on glucagon secretion from isolated mouse islets and alpha tumor cell 1 clone 6 cells (alpha TC1-6 cells). Glucagon release was measured with different saturated and unsaturated fatty acids as well as cis and trans isomers of fatty acids at low and high glucose. Palmitate (0.1-0.5 mmol/L) immediately stimulated glucagon release in a dose-dependent manner from both isolated islets and alpha TC 1-6 cells. The longer chain length of saturated fatty acids, the higher glucagon responses were obtained. The average fold increase in glucagon to saturated fatty acids (0.3 mmol/L) compared to control was octanoate 1.5, laurate 2.0, myristate 2.9, palmitate 5.4, and stearate 6.2, respectively. Saturated fatty acids were more effective than unsaturated fatty acids in stimulating glucagon secretion. At an equimolar concentration, trans-fatty acids were more potent than their cis isomers. Fatty acids immediately stimulate glucagon secretion from isolated mouse islets pancreatic alpha cells. The chain length, spatial configuration, and degree of unsaturation of fatty acids influence the glucagonotropic effect.

The diterpene glycoside, rebaudioside A, does not improve glycemic control or affect blood pressure after eight weeks treatment in the Goto-Kakizaki rat.

The plant, Stevia rebaudiana Bertoni (SrB), has been used for the treatment of diabetes in traditional medicine. Previously, we have demonstrated that long-term administration of the glycoside stevioside has insulinotropic, glucagonostatic, anti-hyperglycemic and blood pressure-lowering effects in type 2 diabetic animal models. The aim of this study was to elucidate if long-term administration of rebaudioside A, another glycoside isolated from the plant SrB, could improve glycemic control and lower blood pressure in an animal model of type 2 diabetes. We divided male Goto-Kakizaki (GK) rats into two groups which were fed a standard laboratory chow diet for eight weeks. The diet was supplemented with oral rebaudioside A (0.025 g/kg BW/day) in the experimental group. Blood glucose, weight, blood pressure and food intake were measured weekly. Animals were equipped with an intra-arterial catheter, and at week eight the conscious rats underwent an intra-arterial glucose tolerance test (IAGTT) (2.0 g/kg BW). During the IAGTT, the level of glucose, glucagon, and insulin responses did not differ significantly between the two groups. Fasting levels of glucose, glucagon, insulin or levels of blood lipids did not differ between the groups throughout the study period. We observed no effect on blood pressure or weight development. In conclusion, oral supplementation with rebaudioside A (0.025 g/kg BW/day) for eight weeks did not influence blood pressure or glycemic control in GK rats. Rebaudioside A failed to show the beneficial effects in diabetic animals previously demonstrated for stevioside.

High-fat feeding during gestation and nursing period have differential effects on the insulin secretory capacity in offspring from normal Wistar rats.

UNLABELLED: Restriction of protein or energy intake during gestation or early life is linked to developmental defects in the endocrine pancreas and insulin resistance. AIMS: To study whether a saturated fatty acid-rich diet during gestation and/or after the weaning period may be detrimental to the insulin secretory capacity later in life. STUDY DESIGN: Female Wistar rats were fed diets rich in carbohydrate (CHO) or saturated fat (SAFA) during pregnancy. The male offspring were split into five subgroups: after birth group 1 (control) continued on CHO and group 3 on SAFA. Group 2 continued on the CHO diet during the nursing period but changed to SAFA post weaning. Group 4 continued on SAFA, but changed to CHO post weaning. For group 5 the offspring of mothers given a SAFA diet were changed to nursing mothers on a CHO diet immediately after birth, and continued on the same diet post weaning. After 14 wk, the islets of Langerhans were isolated for determination of insulin secretory capacity in static incubation and dynamic perifusion experiments. RESULTS: We found a negative correlation (Coef: -3.1, 95% CI: -6.1 to -0.0, p < 0.05) between a diet rich in saturated fat fed to mothers during gestation and a positive correlation (Coef: 4.4, 95% CI: 0.9 to 7.8, p = 0.01) between nursing mothers' diet and the capability to secrete insulin in the offspring. CONCLUSION: Our results indicate the importance of applying a nutrient-balanced diet during pregnancy and the nursing period on the later insulin secretory capacity in the offspring.