It is well known that short-term
growth hormone (GH) administration in humans and animals induces
insulin resistance and
glucose intolerance. The purpose of the present study was to clarify whether
troglitazone, a new
insulin-sensitizing
drug of the
thiazolidinedione class, counteracts the
insulin antagonistic effects of recombinant human (rh) GH on
glucose metabolism in rats. Male Wistar rats weighing 184 to 226 g were treated either with rhGH (n = 8) or rhGH plus
troglitazone (n = 8). rhGH (20 IU/kg
body weight/d) was given by
subcutaneous injection twice daily for 2 days.
Troglitazone was given at 100 mg/kg/d orally for 5 days before and 2 days during rhGH. Saline was injected to the control rats (n = 7). Euglycemic clamp studies with an
insulin infusion rate of 8 mU/kg/min were performed in these rats after an overnight fast. Hepatic
glucose output (HGO),
glucose infusion rate (GIR), and
glucose disappearance rate (GDR) were measured. Fasting levels of plasma
glucose (6.6 +/- 0.1, 6.1 +/- 0.3, 6.5 +/- 0.2 mmol/L),
insulin (187.5 +/- 24.1, 206.4 +/- 24.1, 182.3 +/- 31.0 pmol/L), and serum
free fatty acid (FFA) (1.58 +/- 0.18, 1.43 +/- 0.16, 1.61 +/- 0.25 mEq/L) were comparable among rats treated with rhGH, rhGH plus
troglitazone, and controls, respectively. Basal HGO was also comparable among the three treatment groups. HGO was suppressed significantly during the hyperinsulinemic
glucose clamp in control rats, but not in rhGH rats. When
troglitazone was coadministered with rhGH, suppressibility of HGO during the
glucose clamp was comparable to that of controls. GIR (13.5 +/- 4.5 v 24.1 +/- 4.1 mg/kg/min) and GDR (18.1 +/- 5.8 v 30.3 +/- 5.2 mg/kg/min) were decreased by rhGH treatment compared with control values. They returned to normal levels in rats treated with both rhGH and
troglitazone (GIR, 22.4 +/- 5.9; GDR, 24.7 +/- 7.1). From these results, it is evident that rhGH treatment impaired
insulin's ability to suppress HGO and stimulate peripheral
glucose utilization.
Troglitazone could block the
insulin antagonistic effects of GH on hepatic
glucose output and peripheral
glucose utilization.