Pancreatic effect of a hypoglycaemic fragment of human growth hormone (hGH 6-13)

Abstract

The pancreatic effect of a hypoglycaemic fragment of human growth hormone containing the amino acid sequence Leu-Ser-Arg-Leu-Phe-Asp-Asn-Ala (hGH 6-13), was investigated. In partially pancreatectomized rats, hGH 6-13 (3 mg/kg body weight) enhanced glucose utilization in blood as demonstrated in intravenous glucose tolerance tests (IVGTTs). However, the basal levels of plasma insulin in the animals were apparently not affected by acute administration of the hGH fragment and only slightly modulated with prolonged hGH fragment treatment. Direct studies with the isolated pancreatic islets from normal and hGH 6-13 treated rats showed that hGH 6-13 did not influence in vitro or ex vivo insulin release in the absence of glucose but significantly potentiated the glucose-induced insulin secretion of the pancreatic islets from treated animals. An increase of 42% in glucose oxidation of the isolated pancreatic islets after exposure to hGH 6-13 was observed. This study reveals significant differences in the molecular mechanism of the hypoglycaemic action between the hGH fragments and orally active sulphonylureas. The findings suggest that the hypoglycaemic hGH fragments, structurally unrelated to sulphonylureas, could be a new group of effective agents to achieve blood glucose normalization without the risk of hyperinsulinaemia, as their pancreatic effect is glucose-dependent.