Glucose uptake and glucose transporter proteins in skeletal muscle from undernourished rats

Abstract

Undernutrition in rats impairs secretion of insulin but maintains glucose normotolerance, because muscle tissue presents an increased insulin-induced glucose uptake. We studied glucose transporters in gastrocnemius muscles from food-restricted and control anesthetized rats under basal and euglycemic hyperinsulinemic conditions. Muscle membranes were prepared by subcellular fractionation in sucrose gradients. Insulin-induced glucose uptake, estimated by a 2-deoxyglucose technique, was increased 4- and 12-fold in control and food-restricted rats, respectively. Muscle insulin receptor was increased, but phosphotyrosine-associated phosphatidylinositol 3-kinase activity stimulated by insulin was lower in undernourished rats, whereas insulin receptor substrate-1 content remained unaltered. The main glucose transporter in the muscle, GLUT-4, was severely reduced albeit more efficiently translocated in response to insulin in food-deprived rats. GLUT-1, GLUT-3, and GLUT-5, minor isoforms in skeletal muscle, were found increased in food-deprived rats. The rise in these minor glucose carriers, as well as the improvement in GLUT-4 recruitment, is probably insufficient to account for the insulin-induced increase in the uptake of glucose in undernourished rats, thereby suggesting possible changes in other steps required for glucose metabolism.

GLUT4 expression and subcellular localization in the intrauterine growth-restricted adult rat female offspring

“…These changes are similar to the increased insulin sensitivity of the nutrient-restricted adult (1,8,9). Thus the effect of postnatal and/or adult undernutrition overshadows or reverses any changes due to in utero nutrient restriction.…”

“…Studies involving severe and prolonged nutrient restriction (calorie or protein restriction) that either spans the entire gestation and postnatal period (8, 34 -38) or the late intrauterine and postnatal life until adulthood (day 70) have demonstrated changes in total and subcellular levels of skeletal muscle and myocardial GLUT4 reflecting enhanced insulin sensitivity (1,10,13). These changes are similar to the increased insulin sensitivity of the nutrient-restricted adult (1,8,9).…”

“…Body weights were assessed longitudinally at days 1,21,35,60,90,150,180, and 240. In addition, at days 60 and 180, animals were deeply anesthetized with inhalational isoflurane to maintain organ blood flow, and various organs/tissues were harvested and weighed on a scale with an accuracy of 0.001 g.…”

“…In addition, various investigators have examined the liver, skeletal muscle, and white adipose tissue (WAT), attempting to unravel the insulin receptor and its signaling system (10,17,34,35,37), the growth hormone-IGF system (59,60), and the insulin-responsive glucose transporter (GLUT4) (1,10,13,21,38) as possible mechanisms underlying the development of type 2 diabetes mellitus. In the adult type 2 diabetic human and animals, aberrations in the expression and/or translocation of the GLUT4 glucose transporter isoform have been observed to cause insulin resistance that is characteristic of this condition (18,30,46).…”

“…In contrast, neonatal and adult nutrient restriction in animals increases insulin sensitivity by increasing GLUT4 gene expression and protein concentrations (9,10). The intrauterine nutrient-restricted adult offspring expresses heterogeneity in perturbations, lending to some controversy (1,13,34,37). We therefore hypothesized that intrauterine nutrient restriction negatively affects GLUT4 gene expression and subcellular distribution in a tissue-specific manner, whereas post-natal nutrient restriction may have a relatively protective effect.…”