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Title: Glucagon secretion by the perfused pancreas of the cold exposed rat : the role of adrenergic mechanisms
Author: Edwards, Christine Ingrid Wyn
ISNI:       0000 0001 3438 6309
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1986
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The aim of this study was primarily to establish the time course effects of chronic cold exposure and associated cold acclimation on glucagon (and insulin) secretion from the pancreatic islets of Langerhans in the rat, and to elucidate the possible adrenergic mechanisms involved in the regulation of glucagon secretion in the cold acclimated animal. The data were obtained by monitoring changes in basal and arginine stimulated glucagon (and insulin) secretion from the isolated perfused rat pancreas using a purpose built perfusion system. The study confirmed that glucagon secretion from the isolated perfused pancreas in response to arginine-stimulation, follows a biphasic pattern. The data indicated that chronic cold exposure results in an enhancement of glucagon secretion during the initial four weeks of cold exposure followed by a return to control levels after six weeks of exposure. Associated measurements of insulin secretion demonstrated a progressive reduction in insulin secretion, and insulin:glucagon molar ratios showed a sustained reduction throughout the cold exposure period studied. It was suggested that the enhanced glucagon and decreased insulin response might be the result of a cold induced increase in sympathetic activity. The disappearance of the enhanced glucagon response after six weeks cold exposure was postulated to be the result of desensitisation of the pancreatic A cell to sympathetic stimulation. Studies using alpha and beta adrenergic antagonists supported this hypothesis, with indications of a removal, after 6 weeks cold exposure, of the inhibitory influence of beta blockade seen in the warm acclimated animal. The studies also indicated an inhibitory effect of alpha blockade after cold acclimation, suggesting that alpha adrenoreceptor stimulation of the A cell may be involved in the regulation of glucagon secretion in the cold acclimated animal. Paradoxically, dose-response studies perfusing the isolated rat pancreas with exogenous noradrenaline were unable to demonstrate a reduced sensitivity of the A cell to noradrenaline, indeed there was some evidence to suggest an increased sensitivity to noradrenaline in the cold acclimated animal, although it is suggested that differential vascular effects of noradrenaline in the pancreas of the cold acclimatad animal may contribute to this paradoxical response. It is concluded that during the process of cold acclimation, the initially enhanced glucagon secretion could contribute to the maintenance of an adequate supply of thermogenic substrates, this response disappearing with continued cold exposure, possibly as the result of changes in islet adrenergic sensitivity. The continued reduction in insulin secretion, resulting in maintained low insulin:glucagon molar ratios, could result in an enhanced tissue sensitivity to the glucogenic and lipolytic actions of glucagon, thus possibly enhancing the processes of glucagon induced substrate mobilisation in the cold acclimated animal.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry