Lys9 for Glu9 substitution in glucagon-like peptide-1(7–36)amide confers dipeptidylpeptidase IV resistance with cellular and metabolic actions similar to those of established antagonists glucagon-like peptide-1(9–36)amide and exendin (9–39)

GLP-1 and related peptides cause concentration-dependent relaxation of rat aorta through a pathway involving KATP and cAMP

“…This insulin-releasing peptide is rapidly degraded in vivo by DPP IV to generate its major plasma metabolite, GLP-1(9-36)amide [18]. GLP-1(9-36)amide is largely devoid of insulin-releasing activity, has lower affinity for the GLP-1 receptor and does not attenuate hyperglycaemic excursion [19][20][21][22][23][24]. Exendin-4 (1-39) is a peptide isolated from the salivary glands of the Gila monster lizard which possesses 53% sequence homology to GLP-1 and is a potent GLP-1 receptor agonist [21].…”

“…Exendin-4 (1-39) is a peptide isolated from the salivary glands of the Gila monster lizard which possesses 53% sequence homology to GLP-1 and is a potent GLP-1 receptor agonist [21]. Exendin (9-39) is a well characterised antagonist of the GLP-1 receptor which has been demonstrated on numerous occasions to block the biological actions of both GLP-1(7-36)amide and exendin-4 (1-39) [20,21,23,[25][26][27]. Indeed, a previous study on the ex vivo vascular actions of GLP-1 reported that exendin (9-39) significantly inhibited GLP-1-induced relaxations in rat femoral artery [16].…”

Hyperglycaemia increases dipeptidyl peptidase IV activity in diabetes mellitus

“…Furthermore, the increase in DPP-IV activity could determine an increase in circulating levels of the inactivated form of the hormone GLP-1(9-36)amide, which is a GLP-1 receptor antagonist [22,23], possibly contributing to hyperglycaemia. The nature of the impaired GLP-1 response in type 2 diabetic patients with mild hyperglycaemia, as well as the relative contribution of the hyperglycaemiainduced elevation of DPP-IV to the reduction in active hormone levels in patients with poor metabolic control, needs further investigation.…”

Novel Glucagon-Like Peptide-1 (GLP-1) Analog (Val8)GLP-1 Results in Significant Improvements of Glucose Tolerance and Pancreatic β-Cell Function after 3-Week Daily Administration in Obese Diabetic (ob/ob) Mice

“…Likewise, long-term treatment with GLP-1 improved the glycemic excursion when the peptide was administered acutely with glucose, although there was no further improvement to the insulin response. The extent to which this reflects possible long-term exposure to the truncated metabolite GLP-1-(9 -36) amide that acts as a weak antagonist at the GLP-1 receptor (Green et al, 2004c) is unknown. However, daily administration of the GLP-1 receptor antagonist, exendin(9 -39) amide mildly impaired glucose homeostasis in normal mice due to changes of insulin secretion (Green et al, 2005).…”