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

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 α-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-Ala2]-GIP(1-30) and [D-Ala2]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-Ala2]GIP(1-30) - and [D-Ala2]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, O2 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-Ala2]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). © 2011 Society for Endocrinology.