Mechanism of growth hormone-induced postprandial carbohydrate intolerance in humans

Abstract

Growth hormone excess can cause postprandial carbohydrate intolerance. To determine the contribution of splanchnic and extrasplanchnic tissues to this process, subjects were fed an isotopically labeled mixed meal after either a 12-h infusion of saline or growth hormone (4 micrograms.kg-1.h-1 [corrected]). Growth hormone infusion resulted in higher glucose and insulin concentrations both before and after meal ingestion. Despite growth hormone-induced hyperglycemia and hyperinsulinemia, postprandial hepatic glucose release and carbon dioxide incorporation into glucose (a qualitative estimate of gluconeogenesis) were similar to those present during saline, suggesting altered hepatic regulation. This was confirmed when glucose was infused in the absence of growth hormone to achieve glucose (and insulin) concentrations comparable to those present during growth hormone infusion. Although growth hormone excess did not alter splanchnic uptake of ingested glucose, it resulted in a fivefold increase in postprandial hepatic glucose release (578 +/- 31 vs. 117 +/- 10 mg.kg-16 h-1, P less than 0.01), less suppression of carbon dioxide incorporation into glucose (-13 +/- 9 vs. -53 +/- 12 mg.kg-1. 6-h-1, P less than 0.01), and lower glucose uptake (1,130 +/- 59 vs. 1,850 +/- 150 mg.kg-1.6 h-1, P less than 0.01). The decrease in postprandial glucose uptake did not appear to be mediated by a change in substrate uptake since postprandial plasma concentrations and forearm balance of lactate, free fatty acids, and ketone bodies did not differ in the presence and absence of growth hormone excess.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of nocturnal changes in growth hormone to alter carbohydrate tolerance the following morning

“…sion of hepatic glucose release and insulin induced stimulation of glucose uptake [34,35]. In the absence of an appropriate compensatory increase in insulin secretion, both cause hyperglycaemia [12,13,25,36]. The effects of physiologic changes in these hormones on carbohydrate metabolism have received less attention.…”

“…Endogenous glucose production was calculated by subtracting the rate of appearance of the ingested glucose from the total systemic rate of appearance [4,30]. The per cent of glucose derived from 14 CO 2 was calculated by dividing the specific activity of [6][7][8][9][10][11][12][13][14] C] glucose by the specific activity of 14 CO 2 and multiplying by 100 [30]. Since the specific activity of phosphoenolpyruvate is not known, this calculation provides a qualitative rather than a quantitative estimate of gluconeogenesis [30±32].…”

“…An excess of growth hormone antagonizes insulin induced suppression of endogenous glucose production and insulin induced stimulation of glucose uptake [5±11]. It also impairs glucose tolerance by increasing postprandial rates of glucose production, gluconeogenesis, and by decreasing postprandial rates of glucose uptake [12,13]. These anti-insulin effects are dose dependent and require several hours to develop after an increase in growth hormone concentration [5±11].…”

“…Growth hormone concentrations vary considerably throughout the day in normal humans [12, 14±21]. Growth hormone concentrations fall when glucose concentrations rise and rise when glucose concentrations fall [12,14]. Increases are observed also in response to stress or exercise [22,23] but perhaps the Diabetologia (1998) 41 Summary To determine whether the increases in growth hormone that occur during sleep alter carbohydrate tolerance the following morning, two groups of volunteers were studied on two occasions.…”

Effects of Growth Hormone on Diurnal Insulin Sensitivity in Normal and Type 2 Diabetic Patients and Animal Models

“…The relatively impaired glucose tolerance observed in the afternoon or the evening is associated with a delayed insulin response to the glucose load, which is probably due to decreased sensitivity of pancreatic β cells to glucose [20]. Growth hormone concentrations are known to vary considerably throughout the day in normal subjects [4,[21][22][23]; however, the physiological role of growth hormone-induced diurnal variation in glucose tolerance and insulin sensitivity remains unclear. Patients with T2DM appear to have a different circadian rhythm for plasma glucose, indicating greater insulin sensitivity in the evening.…”