The Minimal Amino Acid Sequence of the Insulin-potentiating Fragments of Human Growth Hormone: Its Mechanism of Action

  1. S Lance Macaulay
  1. Department of Biochemistry, Monash University Clayton, Victoria 3168, Australia
  1. Address reprint requests to J. Bomstein at the above address.

Abstract

A series of synthetic peptides corresponding to the amino-terminal sequence of human growth hormone (hGH) has been studied for insulin-potentiating effects using three different bioassay systems: (1) intravenous insulin tolerance tests, (2) insulin binding to specific receptors of hepatic plasma membranes and isolated hepatocytes, and (3) modulation of insulindependent glycogen synthase and glycogen phosphorylase in muscle and adipose tissue. The results establish that the minimum active sequence is the hexapeptide (hGH 8-13) containing H2N-Arg-Leu-Phe-Asp-Asn-Ala-COOH and strongly indicate that the insulin- potentiating action of the active peptides is to increase the binding of insulin tospecific receptors and thus modulate the action of glycogen synthase and phosphorylase, producing hypoglycemia as the result of increased glycogen storage in liver, muscle, and adipose tissue.

  • Received January 2, 1980.
  • Revision received April 8, 1980.
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