title: 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-Ala²]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).
authors.affiliation: School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes, University of Ulster, Coleraine BT52 1SA, UK.
authors.forename: Victor A
authors.initials: VA
authors.lastname: Gault
authors.forename: David W
authors.initials: DW
authors.lastname: Porter
authors.forename: Nigel
authors.initials: N
authors.lastname: Irwin
authors.forename: Peter R
authors.initials: PR
authors.lastname: Flatt
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002245:Carbon Dioxide / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005749:Gastric Inhibitory Polypeptide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008055:Lipids / Q000097:blood; D008297:Male; D051379:Mice; D010101:Oxygen Consumption / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D010805:Physical Conditioning, Animal
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D010446:Peptide Fragments; C549099:gastric inhibitory polypeptide (1-30); C101760:gastric inhibitory polypeptide (1-42); D002245:Carbon Dioxide; D005749:Gastric Inhibitory Polypeptide