Thesis (Ph.D.)--University of Melbourne, Dept. of Physiology, 2002. / Typescript (photocopy). Includes bibliographical references (leaves 268-306).

Thesis (Ph. D.)-- University of Sydney, 1999. / Title from title screen (viewed Apr. 21, 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Depts. of Psychological Medicine and Medicine. Includes tables. Includes bibliography. Also available in print form.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1984. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 10 uppsatser.

Thesis (Ph.D.) -- University of Adelaide, Dept. of Medicine, 2000. / Bibliography: leaves 206-251.

Habilitationsschrift--Halle-Wittenberg. / At head of title: Aus der Königl. chirurgischen Universitẗs-Klinik Halle.

Thesis (Ph.D.)--University of Wisconsin--Madison, 1978. / Typescript. Vita. Description based on print version record. Includes bibliographies.

Thesis--University of Wisconsin--Madison. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 203-227).

The dual objectives of this thesis were to study the physiological role of GIP in the enteroinsular axis and to chemically characterize a side fraction identified in the purification of GIP. In the physiological studies, the dependency of the insulinotropic action of GIP on the prevailing state of glycaemia was confirmed in dogs using a system of steady state hyperglycaemia. GIP, from both exogenous and endogenous sources, was demonstrated to potentiate insulin release in the presence of moderate hyperglycaemia. Both glucose and fat administered enterally released immunoreactive-GIP (IR-GIP) and potentiated immunoreactive insulin (IRI) release during moderate hyperglycaemia (150 mg% above basal). Intravenous administration of GIP at 2.0 μg/kq.h was also capable of eliciting insulinotropic action during moderate hyperglycaemia. A mixture of ten amino acids was demonstrated to potentiate insulin release with mild hyperglycaemia (40 mg% above fasting) regardless of routes (intravenous, intraduodenal and oral) of administration. However, the release of IR-GIP was not demonstrated following the administration of the amino acid mixture. Arginine and alanine infused individually did not potentiate insulin release in the presence of mild hyperglycaemia. Intraduodenal hydrochloric acid infusion was also demonstrated not to release IR-GIP in the presence of mild hyperglycaemia. The interactions of GIP with tricarboxylic acid cycle intermediates and pyruvate were studied in euglycaemic conditions in dogs. Intravenous administration of individual metabolites (a-ketoglutaric acid, succinate and pyruvate) on an equimolar basis were shown not to be insulinotropic in the presence or the absence of concurrent GIP infusion (0.4 μg/kg.h). The presence of a minor peptide component in the stage III GIP was initially identified by thin layer chromatography. Confirmation of the presence of this minor component was obtained from polyacrylamide-urea gel. These techniques were unsuitable for preparative separation, as were conventional gel filtration and ion exchange separation. Further purification of GIP on high pressure liquid chromatography indicated the presence of a 5% minor peptide component which was eventually shown to contain two less amino acid residues (tyrosine and alanine) than GIP. The amino acid sequence of GIP III indicated the presence of a peptide component with an amino acid sequence different from GIP in that the first two amino acid residues of the N-terminal portion of the molecule (tyrosine and alanine) were missing. The lack of inhibitory activity to pentagastrin-stimulated acid secretion by synthetic GIP led to a reinvestigation of the amino, acid sequence of the molecule. The work in collaboration with Jornvall (Sweden) indicated an error, in that the original sequence included a second glutamine in position 30. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

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