Acute effects of insulin-like growth factor I and insulin on glucose metabolism in vivo

Abstract

We have compared the actions of insulin-like growth factor (IGF-I) and insulin on glucose metabolism in vivo, using the glucose clamp technique in rats. Both hormones caused dose-dependent inhibition of hepatic glucose production, stimulation of whole body glucose disposal, and an increase in the glucose metabolic rate of specific muscles. Infusion of IGF-I also decreased the plasma concentration of insulin. An an infusion rate of 0.57 nmol.kg-1.min-1, IGF-I led to stimulation of whole body glucose uptake that was similar to the glucose uptake produced by infusion of 0.01 nmol.kg-1.min-1 insulin. The glucose metabolic rate, as measured by 2-deoxy-D-glucose uptake, was comparable in quadriceps femoris, soleus, and diaphragm muscles during the infusion of 0.57 nmol.kg-1.min-1 IGF-I and 0.01 nmol.kg-1.min-1 insulin. However, at these rates of infusion, IGF-I caused only a 38 +/- 6% inhibition of hepatic glucose output compared with 66 +/- 12% inhibition by insulin (P less than 0.05). Thus, under these conditions, muscle is more responsive than liver to IGF-I, which agrees with the complement of IGF-I receptors in the two tissues.

Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor I

“…There are few comparable large-animal studies with variants of IGF-I, but a study on pigs [13] has demonstrated that, although IGF-I had no effect on intake when infused for 90 h, both the N-terminally modified IGF-I variants, R3IGF-I and LR3IGF-I, resulted in a 240% decrease in voluntary food intake. This was a higher proportional and faster response than in the present study on sheep, which may reflect differences in species sensitivity or dose-rate differences, because the pigs received 7 ,tg/kg per h compared with the 1.2 ,tg/kg per h used in this study.…”

“…This suggests a direct response of insulin to circulating LR3IGF-I which over-rides any response to the initial reduction in endogenous IGF-I. A direct effect of IGF-I on insulin is reported in other studies by which treatment with IGF-I reduces plasma insulin concentrations when euglycaemia is maintained in dogs [6], rats [7], humans [8] and, in association with an increase in plasma glucose, sheep [14].…”

“…There was a trend for voluntary food intake of the LR3IGF-I-treated group to decline about [5][6][7] days after the start of LR3IGF-I treatment (the intakes of control sheep were paired to the intakes of the LR3IGF-Iinfused sheep) but in most cases intakes returned to 900-1000 g of chaff/day by 10 days of treatment. This level of the intake is approximately 1.2 x maintenance in sheep weighing [30][31][32][33][34][35] kg.…”

“…As well as the somatogenic effects of IGF-I, acute studies have demonstrated insulin-like effects of IGF-I on glucose metabolism, resulting in inhibition of hepatic glucose production, stimulation of whole-body glucose disposal and an increase in the glucosemetabolic rate of muscles in rats [7], with similar effects in humans [8]. The studies with dogs [6] suggest that these insulinlike effects are unrelated to any somatogenic alterations of amino acid exchange between the peripheral tissues and the liver.…”

A Case of Non-Insulin Dependent Diabetes Mellitus with Antiinsulin Antibody: Effect of Subcutaneous Injection of Human Recombinant Insulin-like Growth Factor-I.

“…These observations are consistent with previous reports [6][7][8], suggesting that the glucoselowering effect of IGF-I is direct and not mediated by endogenous insulin secretion. While the possibility of IGF-I having a direct effect on insulin secretion has been suggested [9,10], the fall in the plasma glucose concentration should also account in part for the decrease in endogenous insulin secretion.…”