Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.662276
Title: Dynamics of insulin secretion
Author: Song, Soon Hoo
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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Abstract:
I undertook four related projects that address the pattern of insulin secretion and the specific mechanisms by which b-cell positively influences these. Project one. Direct measurement of the pattern of insulin release in the portal vein (immediately downstream of the pancreas) in human subjects in the basal state and in response to glucose stimulation. Project two. Examination of the effects of acute inhibition of insulin secretion in humans with Type 2 diabetes mellitus by diazoxide on the pattern of insulin secretion. Project three. Development and validation of a method to quantify pulsatile insulin release by cultured human islets in an open loop perifusion system. Project four. Use of the system developed and validated in project 3 to test the hypothesis that transient b-cell rest in human islets induced by diazoxide (inhibiting insulin secretion by opening b cell potassium channels) prevents loss of the first phase insulin release and pulsatile insulin secretion caused by culture of the islets in glucose concentrations comparable to those seen in Type 2 diabetes mellitus. In these experiments, the following observations were made; (1) when insulin secretion was measured, in humans directly in the portal circulation, hyperglycaemia enhanced insulin secretion through the specific mechanism of amplification of the secretory burst mass while the insulin pulse frequency remained unchanged. (2) Acute partial inhibition of insulin secretion by diazoxide in patients with Type 2 diabetes mellitus did not effect the regularity of insulin secretion but did decrease the insulin clearance rate. (3) A deconvolution programme was established that was able to detect 90% of insulin pulses delivered by single human islets. (4). Using the novel islet perfusion system it was possible to show that human islets cultured at high glucose concentrations lost first phase insulin secretion and insulin pulse amplitude but these were restored in islets exposed to a transient period of b-cell rest. The overall conclusion of these studies is that the dynamics of insulin secretion are important as well as the absolute secretion rate and that the abnormalities in these dynamics may be related in part to b cell insulin stores that can be manipulated by transient b cell rest.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.662276  DOI: Not available
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