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Metabolic effects of activation of CCK receptor signaling pathways by twice daily administration of the enzyme resistant CCK-8 analogue, (pGlu-Gln)-CCK-8, in normal mice.

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Irwin, Nigel, Frizzelle, P, O'Harte, Finbarr and Flatt, Peter (2013) Metabolic effects of activation of CCK receptor signaling pathways by twice daily administration of the enzyme resistant CCK-8 analogue, (pGlu-Gln)-CCK-8, in normal mice. Journal of Endocrinology, 216 (1). pp. 53-59. [Journal article]

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DOI: 10.1530/JOE-12-0353

Abstract

Cholecystokinin (CCK) is a hormone that has important physiological effects on energy balance. This study has utilized a stable CCK1 receptor agonist, (pGlu-Gln)-CCK-8, to evaluate the metabolic effects of prolonged administration in normal mice. Twice daily injection of (pGlu-Gln)-CCK-8 for 28 days resulted in significantly lowered body weights (P<0.05) on days 24 and 28 which was associated with decreased accumulated calorie intake (P<0.01) from day 12 onwards. Non-fasting plasma glucose was significantly reduced (P<0.05) on day 28, whilst plasma insulin concentrations were increased (P<0.05). After 28 days, glucose tolerance and glucose-mediated insulin secretion was not significantly different in (pGlu-Gln)-CCK-8 treated mice. However, following a 15 min refeeding period in 18 h fasted mice, glucose levels were significantly (P<0.05) decreased by (pGlu-Gln)-CCK-8 despite similar food intake and nutrient-induced insulin levels. Insulin sensitivity in (pGlu-Gln)-CCK-8 treated mice was significantly (P<0.01) improved compared with controls. Accumulation of triacylglycerol in liver was reduced (P<0.01) but there were no differences in circulating cholesterol and triacylglycerol concentrations, as well as triacylglycerol content of pancreatic, muscle and adipose tissue in (pGlu-Gln)-CCK-8 mice. These data highlight the beneficial metabolic effects of prolonged (pGlu-Gln)-CCK-8 administration and confirm lack of detrimental effects.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:24108
Deposited By:Dr Nigel Irwin
Deposited On:16 Nov 2012 11:21
Last Modified:31 Jan 2013 15:33

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