Glucose-dependent insulinotropic polypeptide (GIP) receptor antagonists as anti-diabetic agents

Publication date: February 2018 Source:Peptides, Volume 100 Author(s): Lærke Smidt Gasbjerg, Maria Buur Nordskov Gabe, Bolette Hartmann, Mikkel Bring Christensen, Filip Krag Knop, Jens Juul Holst, Mette Marie Rosenkilde Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone with a broad range of physiological actions. In the postprandial state, the hormone stimulates insulin secretion and during eu- and hypoglycemia, it stimulates glucagon secretion. In addition, GIP increases triacylglycerol (TAG) uptake in adipose tissue and decreases bone resorption. However, the importance of these actions in humans are not clearly understood as a specific GIP receptor (GIPR) antagonist – an essential tool to study GIP physiology – has been missing. Several different GIPR antagonists have been identified comprising both peptides, vaccines against GIP, GIP antibodies or antibodies against the GIPR. However, most of these have only been tested in rodents. In vitro, N- and C-terminally truncated GIP variants are potent and efficacious GIPR antagonists. Recently, GIP(3–30)NH2, a naturally occurring peptide, was shown to block the GIPR in humans and decrease GIP-induced insulin secretion as well as adipose tissue blood flow and TAG uptake. So far, there are no studies with a GIPR antagonist in patients with type 2 diabetes (T2D), but because the elevations in fasting plasma glucagon and paradoxical postprandial glucagon excursions, seen in patients with T2D...
Source: Peptides - Category: Biochemistry Source Type: research