Effects of recombinant human insulin-like growth factor I and insulin on counterregulation during acute plasma glucose decrements in normal and Type 2 (non-insulin-dependent) diabetic subjects

Abstract

Insulin-like growth factor I (65 micrograms/kg) or insulin (0.1 IU/kg) were injected i.v. on two separate occasions in random order in normal and in Type 2 (non-insulin-dependent) diabetic subjects. Insulin-like growth factor I and insulin injection resulted in identical decrements of plasma glucose concentrations after 30 min but in delayed recovery after insulin-like growth factor I as compared to insulin in both groups (p < 0.05 insulin-like growth factor I vs insulin). Counterregulatory increases in plasma glucagon, adrenaline, cortisol and growth hormone concentrations after hypoglycaemia (1.9 +/- 0.2 mmol/l) in normal subjects were blunted after insulin-like growth factor I administration compared to insulin (p < 0.05). Plasma glucose in Type 2 diabetic subjects did not reach hypoglycaemic levels but the acute glucose decrease to 4.5 +/- 0.8 mmol/l was associated with significantly lower responses of plasma glucagon and adrenaline but higher cortisol levels after insulin-like growth factor I compared to insulin (p < 0.003). Plasma concentrations of non-esterified fatty acids and leucine decreased similarly after insulin-like growth factor I and insulin in both groups. The present results demonstrate that insulin-like growth factor I is capable of mimicking the acute effects of insulin on metabolic substrates (plasma glucose, non-esterified fatty acids, leucine). The decreases of plasma glucose were similar after both peptides in normal and in diabetic subjects who were presumably insulin resistant. Counterregulatory hormone responses to plasma glucose decrements differed, however, between insulin-like growth factor I and insulin and in the diabetic and the control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of insulin‐like growth factor‐I and its binding proteins in glucose homeostasis and type 2 diabetes

“…Specifically, in vitro studies have shown that IGF-I may have insulin-like effects in promoting the uptake of free fatty acids (FFA) into adipocytes, hepatocytes, and other tissues, and secondly, in promoting lipogenesis [83,122]. Consistent with this, several human studies [12,83,123,124], albeit, not all [11,33,72], reported that exogenous IGF-I administration significantly lowered serum FFA levels. In one typical study, for example, recombinant IGF-I administration reduced serum FFA levels from a mean of 411 ± 58 µM at baseline to just 165 ± 36 µM ( p < 0.001), with similar effects observed among patients with and without type 2 diabetes [83].…”

Free insulin-like growth factors – measurements and relationships to growth hormone secretion and glucose homeostasis

“…This hypothesis has been corroborated by clinical trials showing that administration of recombinant human (rh)-IGF-I improves insulin sensitivity and hyperglycemia in patients suffering from type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM) as well as severe insulin resistance [18][19][20][21]. However, the possible role of endogenous IGF-I in glucose homeostasis remains to be clarified.…”

“…IGF-I treatment lowers plasma glucose in healthy subjects, in patients with T1DM and T2DM and even in patients suffering from severe insulin resistance due to mutations in the insulin receptor (IR) gene (type A diabetes) [18][19][20]217,218]. The glucose lowering effect of IGF-I is mediated through an increased peripheral glucose uptake and glycogen synthesis in skeletal muscles, as well as a suppression of the hepatic glucose production (HGP).…”

Effect of IGF-I on FFA and glucose metabolism in control and type 2 diabetic subjects

“…The acute effects of IGF-I on peripheral and hepatic glucose metabolism in type 2 diabetic humans have been less well characterized. Laagerand and Keller (26) demonstrated that the decline in plasma glucose concentration in response to intravenous IGF-I was impaired in type 2 diabetic individuals, but this study did not examine whether the IGF-I resistance was present in skeletal muscle, in liver, or in both. In a previous study (7), we demonstrated that chronic subcutaneous IGF-I administration in type 2 diabetic patients inhibited EGP, reduced the fasting glucose concentration, and produced a small increase in insulin-mediated glucose disposal.…”