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Hypothalamic peptides in the regulation of feeding and peripheral metabolism

Meeran, Mohammed Karim; (1997) Hypothalamic peptides in the regulation of feeding and peripheral metabolism. Doctoral thesis (M.D), UCL (University College London). Green open access

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The central nervous system is essential to the normal control of metabolic processes. Maintenance of energy balance is an important part of homeostasis and involves the control of food intake (input) and of peripheral metabolism (output). Loss of this homeostatic mechanism can lead to either obesity or cachexia. Neuropeptide Y (NPY) is a 36 amino acid peptide that is found in several hypothalamic regions involved in the control of food intake. It potently stimulates feeding following intracerebroventricular (ICV) injection. In addition it has several effects on peripheral metabolism including stimulation of ACTH release from the pituitary gland and an increase in peripheral insulin resistance. Using analogues of NPY with differential binding to the known NPY receptors, I have shown that there are at least two novel central NPY receptors that mediate these effects of NPY. I have shown that a recently discovered NPY receptor antagonist, BIBP 3226 inhibits NPY induced feeding but that it has no effect on NPY mediated stimulation of ACTH release. It has been postulated that foetal malnutrition can program peripheral glucose metabolism in later life. I have studied the effects of early malnutrition on pregnant and weanling rats and have shown that such programming does not occur at the level of hypothalamic neuropeptide Y messenger RNA. I have also shown that glucagon like peptide-1 (CLP-1) is a novel central satiety factor, and that chronic blockade of GLP-1 receptors can lead to an increase in weight of rats. In addition I have shown that the effects of ICV GLP-1 as a satiety factor do not occur by any change in hypothalamic NPY, suggesting that the GLP-1 satiety system works independently of NPY. I have also shown that ICV GLP-1 causes a fall in peripheral plasma glucose and insulin concentrations, suggesting that central GLP-1 may have a role in the modulation of peripheral insulin sensitivity.

Type: Thesis (Doctoral)
Qualification: M.D
Title: Hypothalamic peptides in the regulation of feeding and peripheral metabolism
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Health and environmental sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10103744
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