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Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice

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

Gault, Victor, Porter, David W., Irwin, Nigel and Flatt, Peter (2011) Comparison of sub-chronic metabolic effects of stable forms of naturally occurring GIP(1-30) and GIP(1-42) in high-fat fed mice. JOURNAL OF ENDOCRINOLOGY, 208 (3). pp. 265-271. [Journal article]

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DOI: 10.1530/JOE-10-0419

Abstract

Glucose-dependent insulinotropic polypeptide (GIP) is a 42 amino acid hormone secreted from intestinal K-cells, which exhibits a number of actions including stimulation of insulin release. A truncated form, GIP(1-30), has recently been demonstrated in intestine and islet alpha-cells. To evaluate the potential physiological significance of this naturally occurring form of GIP, the present study has examined and compared the bioactivity of enzymatically stabilised forms, [D-Ala(2)]-GIP(1-30) and [D-Ala(2)]GIP(1-42), in high-fat fed mice. Twice-daily injection of GIP peptides for 42 days had no significant effect on food intake or body weight. However, non-fasting glucose levels were significantly lowered, and insulin levels were elevated in both treatment groups compared to saline controls. The glycaemic response to i.p. glucose was correspondingly improved (P < 0.05) in [D-Ala(2)]GIP(1-30)- and [D-Ala(2)]GIP(1-42)-treated mice. Furthermore, glucose-stimulated plasma insulin levels were significantly elevated in both treatment groups compared to control mice. Insulin sensitivity was not significantly different between any of the groups. Similarly, plasma lipid profile, O-2 consumption, CO2 production, respiratory exchange ratio, and energy expenditure were not altered by 42 days twice-daily treatment with [D-Ala(2)]GIP(1-30) or [D-Ala(2)]GIP(1-42). In contrast, ambulatory activity was significantly (P < 0.05) elevated during the light phase in both GIP treatment groups compared to saline controls. The results reveal that sustained GIP receptor activation exerts a spectrum of beneficial metabolic effects in high-fat fed mice. However, no differences were discernable between the biological actions of the enzyme-resistant analogues of the naturally occurring forms, GIP(1-30) and GIP(1-42). Journal of Endocrinology (2011) 208, 265-271

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:18872
Deposited By:Dr Nigel Irwin
Deposited On:30 Jun 2011 13:46
Last Modified:19 Nov 2012 15:36

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