Chronic growth hormone treatment in normal rats reduces post-prandial skeletal muscle plasma membrane GLUT1 content, but not glucose transport or GLUT4 expression and localization

Abstract

Whether skeletal muscle glucose transport system is impaired in the basal, post-prandial state during chronic growth hormone treatment is unknown. The current study was designed to determine whether 4 weeks of human growth hormone (hGH) treatment (3.5 mg\kg per day) would impair glucose transport and\or the number of glucose transporters in plasma membrane vesicles isolated from hindlimb skeletal muscle of SpragueDawley rats under basal, post-prandial conditions. hGH treatment was shown to have no effect on glucose influx (V max or K m ) determined under equilibrium exchange conditions in isolated plasma membrane vesicles. Plasma membrane glucose transporter number (R o ) measured by cytochalasin B binding was also unchanged by hGH treatment. Consequently, glucose transporter turnover number (V max \R o ), a measure of average glucose transporter intrinsic activity, was similar in hGH-treated and

The role of growth hormone and glucocorticoid in glucose handling in vivo

“…Until this type of data are presented we have to conclude that the combined administration of GH and MP does not generally decrease peripheral insulin-stimulated glucose disposal. Such a conclusion is further supported by the fact that neither GH (Cartee & Bohn 1995, Napoli et al 1996 nor dexamethasone (Haber & Weinstein 1992, Venkatesan et al 1996, Dimitriadis et al 1997 change the abundance of the glucose transporter molecule GLUT-4 in muscle cell membranes.…”

“…This would shift the dose-response curve to the right, but not alter the maximal effect of insulin, as not all receptors are needed to attain the maximum response (DeFronzo 1982). Such a reasoning could perhaps explain why neither GH (Dimitriadis et al 1994, Cartee & Bohn 1995, Napoli et al 1996 nor glucocorticoid (Dimitriadis et al 1997) reduce in vitro glucose transport activity in muscle during maximal insulin stimulation. However, to elucidate this issue further in vivo dose-response curves of insulin-stimulated glucose uptake in rats treated with GH and/or glucocorticoid are required.…”

Effects of prolonged fasting and sustained lipolysis on insulin secretion and insulin sensitivity in normal subjects

“…The dynamics of the insulin response also appeared to be different, because the 24-h fast induced marked reductions in p 3 and p 2 , suggesting a decreased rate of provision of insulin action, and a delayed onset but prolonged duration of insulin action. This could indicate a slowdown in the insulin signaling cascade due to enhanced activation of the GH receptor, which shares intracellular substrates with the insulin receptor (14,35,48). However, only the decrease in p 3 correlated with the increase in GH levels during the prolonged fast, and Nielsen et al (37) recently showed that there appears to be no cross-talk between the GH receptor and insulin signaling pathway in humans.…”

“…During the IVGTT, blood samples for GH were taken every 15 min until 1100 and for FFA at 0810, 0819, 0830, 0845, 0900, 0930, 1000, 1030, and 1100. Glucose and insulin levels were measured 2, 3,4,5,6,8,10,15,19,22,23,25,27,30,35,40,60,90,120,150, and 180 min after the intravenous glucose bolus. Subjects were then given breakfast, and both cannulas were removed before subjects were discharged from the research unit.…”

The metabolic role of growth hormone in humans with particular reference to fasting

“…This concept is supported by a rat study [150] in which the induction of insulin resistance was preceded by suppression of glycogen synthesis. On the other hand, studies in rat muscle [147,151] demonstrate that in vivo exposure to GH is associated with an increased abundance of insulin receptors but diminished basal and insulin-stimulated phosphorylation of the insulin receptor. The impact of GH on GLUT 4 translocation has not yet been studied in humans.…”