Return to search

On the mechanism of action of glucose-dependent insulinotropic polypeptide

The interaction of the intestinal insulinotropic hormone GIP (Glucose-dependent Insulinotropic Polypeptide or Gastric Inhibitory Polypeptide) with the stimulus-secretion coupling mechanism of glucose-induced insulin secretion was investigated using the isolated, perfused, rat pancreas technique. The action of GIP in potentiating insulin secretion which had been initiated by a number of metabolic compounds other than glucose (D-glycer-aldehyde, 2-ketoisocaproate, L-leucine + L-glutamine) and the concentration-dependent nature of this action led to the formulation
of the hypothesis that the insulinotropic effect of GIP required prior oxidation of these insulin-stimulating metabolites. It was therefore likely that the mechanism whereby GIP potentiated glucose-induced insulin secretion required an interaction located at a level involving effects secondary to glucose degradation in the B-cell. This effect may have required an intact N-terminus on the GIP molecule since a GIP₃-₄₂ homologue, which lacked the N-terminal Tyrosine-Alanine, possessed greatly diminished insulinotropic
activity. Additional biological actions of GIP were suggested by the stimulation by the hormone of pancreatic somatostatin
release and of the release of lipoprotein lipase-like activity from isolated rat adipocytes.
A technique using reversed phase high pressure liquid
chromatography (HPLC) was developed allowing the purification and
fodination-state analysis of a pure bioactive ¹²⁵I-GIP molecule.
Preliminary investigations of receptor binding activity of this purified ¹²⁵I-GIP to isolated rat adipocytes were also performed. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Identiferoai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/24281
Date January 1983
CreatorsDahl, Marshall Andrew
PublisherUniversity of British Columbia
Source SetsUniversity of British Columbia
LanguageEnglish
Detected LanguageEnglish
TypeText, Thesis/Dissertation
RightsFor non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

Page generated in 0.0017 seconds