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Beneficial Effects of (pGlu-Gln)-CCK-8 on Energy Intake and Metabolism in High Fat Fed Mice are Associated with Alterations of Hypothalamic Gene Expression.

Montgomery, IA, Irwin, Nigel and Flatt, Peter (2013) Beneficial Effects of (pGlu-Gln)-CCK-8 on Energy Intake and Metabolism in High Fat Fed Mice are Associated with Alterations of Hypothalamic Gene Expression. Hormone and Metabolic Research, 45 (6). pp. 471-473. [Journal article]

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DOI: 10.1055/s-0032-1331767

Abstract

Cholecystokinin (CCK) is a gastrointestinal hormone with potential therapeutic promise for obesity-diabetes. The present study examined the effects of twice daily administration of the N-terminally modified stable CCK-8 analogue, (pGlu-Gln)-CCK-8, on metabolic control and hypothalamic gene expression in high fat fed mice. Sub-chronic twice daily injection of (pGlu-Gln)-CCK-8 for 16 days significantly decreased body weight (p<0.05), energy intake (p<0.01), circulating blood glucose (p<0.001), and plasma insulin (p<0.001) compared to high fat controls. Furthermore, (pGlu-Gln)-CCK-8 markedly improved glucose tolerance (p<0.05) and insulin sensitivity (p<0.05). Assessment of hypothalamic gene expression on day 16 revealed significantly elevated NPY (p<0.05) and reduced POMC (p<0.05) and MC4R (p<0.05) mRNA expression in (pGlu-Gln)-CCK-8 treated mice. High fat feeding or (pGlu-Gln)-CCK-8 treatment had no significant effects on hypothalamic gene expression of receptors for leptin, CCK1 and GLP-1. These studies underscore the potential of (pGlu-Gln)-CCK-8 for the treatment of obesity-diabetes and suggest modulation of NPY and melanocortin related pathways may be involved in the observed beneficial effects.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Faculty of Life and Health Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:24833
Deposited By: Dr Nigel Irwin
Deposited On:05 Feb 2013 10:21
Last Modified:10 Jun 2013 09:33

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