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Prolonged effect of insulin on glucose uptake by rat skeletal muscle.

ABSTRACT: The fate of insulin, as it relates to its action on skeletal-muscle glucose uptake, was studied in non-cyclically perfused rat hindlimbs. Insulin (1m-i.u./ml) with and without (125)I-labelled insulin was infused intra-arterially for 5 or 6min. Net glucose uptake and the release of (125)I-labelled insulin into the venous effluent were evaluated by arteriovenous-difference measurements for an additional 24-32min. The infusion of insulin for 5min promoted glucose uptake, an effect that persisted throughout a subsequent 25min of perfusion in the absence of insulin. The addition of insulin antibody to the perfusate in the presence of insulin blocked the action of insulin on glucose uptake, but it failed to alter insulin action if the muscle tissue had been exposed to insulin before addition of antibody. When (125)I-labelled albumin was infused for 6min, venous effluent radioactivity decayed rapidly and remained HClO(4)-insoluble and there was no significant tissue retension of radioactivity. Comparable experiments in which (125)I-labelled insulin was infused for 6min revealed that the venous effluent radioactivity decayed more slowly, a significant amount of the (125)I-labelled insulin appeared as fragments (HClO(4)-soluble) and there was a significant retention of radioactivity in the tissue. Radioactivity in muscle tissue biopsies obtained 28min after infusion of (125)I-labelled insulin was associated largely with intact insulin and a peptide of mol.wt. 2400. The total radioactivity retained in the muscle at this time was 7% of the amount infused. An insulin bolus (1i.u.) failed to increase the discharge of this tissue-associated radioactivity. These results suggest that insulin and a product of insulin metabolism persists in muscle tissue long after the arterial presence of insulin ends. This tissue residence and processing of insulin may be important components of insulin's prolonged action on glucose uptake by skeletal muscle.

SUBMITTER: Lewis SB

PROVIDER: S-EPMC1161708 | biostudies-other | 1980 Mar

REPOSITORIES: biostudies-other

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Project description:Key pointsPaternal obesity negatively influences metabolic outcomes in adult rat offspring. Maternal voluntary physical activity has previously been reported to improve glucose metabolism in adult rat offspring sired by healthy fathers. Here, we investigated whether a structured programme of maternal exercise training before and during gestation can attenuate the negative impacts that paternal obesity has on insulin sensitivity and secretion in female adult offspring. Exercise before and during pregnancy normalised the lower insulin sensitivity in skeletal muscle and the lower insulin secretion observed in female offspring sired by obese fathers. This paper presents a feasible, low-cost and translatable intervention strategy that can be applied perinatally to support multifactor interventions to break the cycle of metabolic dysfunction caused by paternal obesity.AbstractWe investigated whether maternal exercise before and during gestation could attenuate the negative metabolic effects of paternal high-fat diet-induced obesity in female adult rat offspring. Fathers consumed a normal chow or high-fat diet before mating. Mothers exercised on a treadmill before and during gestation or remained sedentary. In adulthood, female offspring were assessed using intraperitoneal insulin and glucose tolerance tests (IPITT and IPGTT, respectively), pancreatic morphology, ex vivo skeletal muscle insulin-stimulated glucose uptake and mitochondrial respiratory function. Paternal obesity impaired whole-body and skeletal muscle insulin sensitivity and insulin secretion in adult offspring. Maternal exercise attenuated the lower insulin-stimulated glucose uptake in offspring sired by obese fathers but distal insulin signalling components (p-AKT Thr308 and Ser473, p-TBC1D4 Thr642 and GLUT4) remained unchanged (P > 0.05). Maternal exercise increased citrate synthase activity only in offspring sired by obese fathers. Maternal exercise also reversed the lower insulin secretion in vivo observed in offspring of obese fathers, probably due to an attenuation of the decrease in pancreatic beta cell mass. In summary, maternal exercise before and during pregnancy in rats attenuated skeletal muscle insulin resistance and attenuated the decrease in pancreatic beta cell mass and insulin secretion observed in the female offspring of obese fathers.

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Prolonged effect of insulin on glucose uptake by rat skeletal muscle.

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