To compare the metabolic effects of elevated plasma concentrations of IGF-I and insulin, overnight-fasted normal subjects were studied twice, once receiving IGF-I and once insulin at doses that resulted in identical increases in glucose uptake during 8-h euglycemic clamping. Recombinant human IGF-I or insulin were infused in one group at high doses (30 l.g/kg per h IGF-I or 0.23 nmol/kg per h insulin) and in another group at low doses (5 gg/kg per h IGF-I or 0.04 nmol/kg per h insulin). Glucose rate of disappearance (measured by 16,6-D21-glucose infusions) increased from baseline by 239±16% during high dose IGF-I vs 197±18% during insulin (P = 0.021 vs IGF-I). Hepatic glucose production decreased by 37±6% during high dose IGF-I vs 89±13% during insulin (P = 0.0028 vs IGF-I). IGF-I suppressed whole body leucine flux (1-1'3C1-leucine infusion technique) more than insulin (42±4 vs 32±3% during high doses, P = 0.0082). Leucine oxidation rate decreased during high dose IGF-I more than during insulin (55±4 vs 32±6%, P = 0.0001). The decreases of plasma concentrations of free fatty acids, acetoacetate, and f8-hydroxybutyrate after 8 h of IGF-I and insulin administration were similar. Plasma C-peptide levels decreased by 57±4% during high doses of IGF-I vs 36±6% during insulin (P = 0.005 vs IGF-I). The present data demonstrate that, compared to insulin, an acute increase in plasma IGF-I levels results in preferential enhancement of peripheral glucose utilization, diminished suppression of hepatic glucose production, augmented decrease of whole body protein breakdown (leucine flux), and of irreversible leucine catabolism but in similar antilipolytic effects. The data suggest that insulin-like effects of IGF-I in humans are mediated in part via IGF-I receptors and in part via insulin receptors. (J. Clin. Invest. 1993. 92:1903-1909

The effect of two isocaloric evening meals (low protein-high fat vs. high protein-low fat content) on plasma glucose regulation during the night were compared. Eight C-peptide-defïcient type-I diabetic subjects without autonomic neuropathy were treated with fixed doses of continuous infusions of insulin during 2 nights. At 7 p.m. they received in random order either a low protein-high fat (5% of total energy protein, 60% fat, 35% carbohydrate) or a high protein-low fat (35% protein, 30% fat, 35% carbohydrate) evening meal. Venous plasma samples were drawn hourly thereafter. Plasma glucose concentrations were similar postprandially during the 2 nights between 7 p.m. and 11 p.m., but they were higher in the early morning hours after the high protein meal (p < 0.02 vs. the low protein meal). Two subjects developed symptomatic hypoglycemia after the low protein meal. Plasma glucagon concentrations were higher (p = 0.023) and serum free insulin lower (p < 0.05) after the high protein-low fat meal. Plasma cortisol and growth hormone were not significantly different between the two diets. Therefore, an increase in the protein content of the evening meal (fat content diminished) increases plasma glucose concentrations several hours later in the night, possibly due to protein-induced glucagon secretion and to lower plasma free insulin levels. Patients with type-I diabetes with a tendency to develop hypoglycemia during the night may avoid this problem by increasing the protein content of the evening meal.

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)

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