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Title: Divergence between the mechanisms of insulin secretion : role of glucagon and neurotensin
Author: Atabani, Ghazi Salahuddin
ISNI:       0000 0001 3431 4217
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 1985
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An immune neutralization in vivo model, using antiglucagon immunoglobulins, was characterized and found to be capable of specifically and effectively blocking A-cell secretion in rats. This was applied to the study of the mechanism of insulin secretion by different secretagogues. Results indicated that arginine and the sulphonylurea drugs acted on the B-cell via glucagon, whereas glucose, leucine and GIP acted directly. Results also supported the possibility of GIP having an incretin effect. Further investigation into the mechanism of insulin secretion was carried out using diazoxide. This drug inhibited the actions of glucose, arginine, leucine and glucagon on the B-cell, but not those of sulphonylureas. This lent support to the general concept of diversity of insulin secretion mechanisms. However the nonspecificity of diazoxide action prevented a precise interpretation of data. A radioimmunoassay for neurotensin was developed in order to evaluate its plasma levels and hence its role in glucose homeostasis and insulin secretion. When applied to the study of fasting and fat-stimulated plasma neurotensin levels of healthy individuals, the assay could not measure any significant changes. Since the assay was specific only to the intact neurotensin molecule, these observations cast doubt on the importance of circulating NT (1-13) levels in post-meal physiology. Infusion studies with synthetic neurotensin were carried out in rats. Results confirmed the hyperglycaemic and hyperglucagonaemic effects of the peptide at the pharmacological doses used. Contrarily, no effect on plasma insulin or somatostatin was observed. Further study of the hyperglycaemic action showed that it was mediated by glucagon.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Biochemistry