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Sensitization of isolated rat islets to stimulation with glucose by prior exposure to glucose-dependent insulinotropic polypeptide (GIP)

University of British Columbia

This thesis describes the relationship between glucose- and glucose dependent insulinotropic polypeptide (GlP)-stimulated insulin release from the pancreatic islet and β cell. Protocols were developed to test the hypothesis that the intact islet contains heterogeneous populations of β cells and that GIP can sensitize these populations to subsequent stimulation by glucose. Changes in intracellular free calcium- concentration in response to glucose or GIP administered prior to glucose were used to test the hypotheses, respectively. Culture conditions were developed which allowed the measurement of free intracellular calcium from individual β cells within the intact islet. Due to technical difficulties and questionable physiological relevance of the islet cultures developed to test these hypotheses, attempts to measure intracellular free calcium were abandoned and the hypotheses not tested. An alternate approach to investigating the relationship between glucose- and GIP-stimulated insulin secretion was developed by measuring insulin secretion from perifused whole islets. Insulin secretion in response to 1 nM GIP administered 1 h immediately prior to 2 h of 11.0 mM glucose was found to be significantly. (p<0.05) greater than that secreted in response to 11.0 mM glucose without prior application of GIP. This priming effect of GIP persisted when the interval between GIP and glucose application was increased to 20 or 40 minutes. No significant difference in the priming and potentiating effects of GIP on glucose-stimulated insulin secretion from islets was observed. Although these studies do not provide direct evidence for the mechanisms of glucose- and GIP-stimulated insulin secretion, they provide indirect evidence for crosstalk between second messengers generated by glucose and GIP within the β cell.

Thesis/Dissertation

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2009-01-14

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http://hdl.handle.net/2429/3628

Physiology

University of British Columbia

UBCV

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