The Effect of Growth Hormone on Splanchnic Glucose and Substrate Metabolism Following Oral Glucose Loading in Healthy Man

Abstract

Elevated plasma concentrations of growth hormone impair glucose tolerance and insulin sensitivity of peripheral tissues. To study the effect of short-term exposure to growth hormone concentrations elevated into the upper physiologic range (7–10 ng/ml) on splanchnic carbohydrate metabolism, both splanchnic glucose output (SGO) and substrate exchange after ingestion of a 75-g glucose load were determined by means of the liver vein catheter technique in six healthy volunteers after growth hormone administration. Growth hormone was infused at a rate of 2 μg/ kg · h starting 120 min before and continuing for 150 min following the glucose load. Control studies without growth hormone administration were performed in seven subjects. SGO was 104 ± 10 (SEM) mg/min in the postabsorptive state and increased to 43.4 ± 2.2 g during the 150-min period following glucose ingestion. Growth hormone infusion did not alter basal SGO (130 ± 14 mg/min), nor the splanchnic exchange of lactate, pyruvate, and free fatty acids, whereas basal production of β-OH-butyrate was increased twofold; following glucose ingestion a higher proportion of the given glucose load escaped the splanchnic bed after growth hormone exposure (66.9 ± 6.8 g/150 min; P < 0.005). The insulin production rate (basal 14 ± 2 mU/min; following oral glucose 7.0 ± 0.8 U/150 min) as calculated from C-peptide release from the splanchnic area was unaltered by growth hormone exposure in the basal state (14 ± 3 mU/min), but augmented after glucose ingestion (14.8 ± 1.5 U/150 min). The higher rate of glucose release by the splanchnic bed after glucose ingestion despite a more marked hyperglycemia and increased insulin secretion suggests that acute elevations of plasma growth hormone within the physiologic range, besides causing insulin resistance of peripheral tissues, affect glucose disposal of splanchnic tissues as well.