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Diabetes. 2017 Sep;66(9):2363-2371. doi: 10.2337/db17-0480. Epub 2017 Jun 30.

The Gluco- and Liporegulatory and Vasodilatory Effects of Glucose-Dependent Insulinotropic Polypeptide (GIP) Are Abolished by an Antagonist of the Human GIP Receptor.

Author information

1
Department of Endocrinology, Bispebjerg University Hospital, Copenhagen, Denmark masmar@sund.ku.dk.
2
Department of Clinical Physiology and Nuclear Medicine, Bispebjerg University Hospital, Copenhagen, Denmark.
3
Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
4
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
5
Xlab, Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark.
6
Department of Geriatrics, Bispebjerg University Hospital, Copenhagen, Denmark.

Abstract

A truncated form of human glucose-dependent insulinotropic polypeptide (GIP), GIP(3-30)NH2, was recently identified as an antagonist of the human GIP receptor. This study examined the ability of GIP(3-30)NH2 to antagonize the physiological actions of GIP in glucose metabolism, subcutaneous abdominal adipose tissue blood flow (ATBF), and lipid metabolism in humans. Eight lean subjects were studied by measuring arteriovenous concentrations of metabolites and ATBF on three different occasions during hyperglycemic-hyperinsulinemic clamps with concomitant infusions of GIP, GIP(3-30)NH2, or both GIP and GIP(3-30)NH2 During infusion of GIP(3-30)NH2 alone and in combination with GIP, insulin levels and the total glucose amount infused to maintain the clamp were lower than during GIP alone. In addition, ATBF remained constant during the antagonist and increased only slightly in combination with GIP, whereas it increased fivefold during GIP alone. Adipose tissue triacylglyceride (TAG) and glucose uptake decreased, and the free fatty acid/glycerol ratio increased during the antagonist alone and in combination with GIP. The changes in glucose infusion rates and plasma insulin levels demonstrate an inhibitory effect of the antagonist on the incretin effect of GIP. In addition, the antagonist inhibited GIP-induced increase in ATBF and decreased the adipose tissue TAG uptake, indicating that GIP also plays a crucial role in lipid metabolism.

PMID:
28667118
DOI:
10.2337/db17-0480
[Indexed for MEDLINE]
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