The role of growth hormone in the glucose intolerance of uremia

Abstract

The fasting plasma growth hormone (GH) concentration and the plasma growth hormone response to sustained hyperglycemia was examined in 8 chronically uremic subjects before and after hemodialysis employing the hyperglycemia clamp technique. The plasma glucose concentration was acutely raised and maintained at +125 mg/100 ml above basal levels. Since the glucose concentration was held constant, the glucose infusion rate is an index of glucose metabolism (M) and M divided by the plasma insulin response (I) is a measure of tissue sensitivity to insulin. Predialysis, the fasting GH concentration, 4.0 +/- 1.0 ng/ml, was significantly greater than controls, 0.3 +/- 0.1 ng/ml (p less than 0.01), and failed to suppress normally following sustained hyperglycemia. Both M, 4.23 +/- 0.36 mg/kg x min, and M/I, 5.05 +/- 0.79 mg/kg x min per microU/ml, were significantly reduced compared to controls (p less than 0.001). There was no correlation between either the fasting GH concentration or the GH response to sustained hyperglycemia and either M or M/I. Following dialysis both M, 6.30 +/- 0.64 mg/kg x min, and M/I, 8.39 +/- 1.06 mg/kg x min per microU/ml, increased (p less than 0.01) without significant change in either the fasting GH level, 4.0 +/- 1.2 ng/ml, or the plasma GH response to hyperglycemia. It is concluded that while deranged GH physiology is a common accompaniment of the uremic state, it is not responsible for the glucose intolerance and tissue insensitivity to insulin observed in uremia.

Effects of Growth Hormone on Insulin Action in Man: Mechanisms of Insulin Resistance, Impaired Suppression of Glucose Production, and Impaired Stimulation of Glucose Utilization

“…Plasma growth hormone concentrations comparable to or in excess of those produced in the present study are frequently found in patients with poorly controlled diabetes mellitus, 49 uremia, 50 and during various stresses. 51 It is therefore possible to speculate that the abnormalities in glucose metabolism associated with these conditions may be explained at least in part by resistance to insulin due to increases in growth hormone secretion.…”

Effect of growth hormone on the response to insulin and glucose turnover in sheep

“…In fed sheep the two major sites of glucose disposal are the portal-drained viscera and skeletal muscle (Weekes 1979). In humans, the portal-drained viscera have been shown to be unresponsive to increased insulin levels with respect to glucose disposal, whilst skeletal muscle was highly sensitive (DeFronzo et al 1979). Growth hormone treatment of dairy cows has been shown to reduce the uptake of glucose across the hind-limb (which is predominantly skeletal muscle) under normal insulin concentrations (McDowell et al 1987).…”

“…Thus, the most important single site for the reduction in glucose utilization following exposure to growth hormone is likely to be skeletal muscle. Hyperinsulinaemia would stimulate skeletal muscle glucose oxidation and glycogen synthesis (DeFronzo et al 1979;Sasaki 1989). Adipose tissue is unlikely to be a significant site for the reduced insulin responsiveness, since in ruminants acetate is the major precursor of adipose long chain fatty acids, not glucose.…”