Glucagonostatic and Insulinotropic Action of Glucagonlike Peptide I-(7–36)-Amide

Abstract

We examined the effect of glucagonlike peptides (GLPs), which are cleaved from preproglucagon in the enteroglucagon cells, on rat endocrine pancreas with the isolated perfused system. GLP-I-(7-36)-amide, a truncated form of full-sequence GLP-I-(1-37), showed a potent inhibitory effect on glucagon secretion. This inhibitory effect of GLP-I-(7-36)-amide was demonstrated at concentrations of 0.25, 2.5, and 25 nM in 11.2 and 2.8 mM glucose. In contrast, insulin release was significantly stimulated by GLP-I-(7-36)-amide at its concentration from 0.025 to 25 nM in a high glucose concentration, whereas in a low glucose concentration, the stimulation was seen only at the highest concentration (25 nM). Neither GLP-I-(1-37) nor GLP-II showed any effect on glucagon and insulin release. Although several gastrointestinal hormones have been nominated as incretins, none of them may suppress the glucagon secretion. A truncated form of GLP-I, GLP-I-(7-36)-amide thus seems to be a unique incretin that exerts glucagonostatic action.

Intracellular Signals Mediating the Food Intake-Suppressive Effects of Hindbrain Glucagon-like Peptide-1 Receptor Activation

“…Accumulating clinical and basic science data suggests that pharmacotherapies targeting the GLP-1 system are ameliorative not only for Type II Diabetes Mellitus (T2DM), but for obesity as well (Lovshin and Drucker, 2009). Interestingly, exogenous activation of either peripheral or central GLP-1 receptors (GLP-1R) produces a comparable profile of physiological responses that include: enhanced glucose-stimulated insulin secretion (Komatsu et al, 1989), inhibition of gastric emptying (Hayes et al, 2008b, c; Imeryuz et al, 1997; Wettergren et al, 1993), and inhibition of food intake (Chelikani et al, 2005; Gutzwiller et al, 1999; Hayes et al, 2009a; Hayes et al, 2008c; Kinzig et al, 2002; Moran et al, 1996; Turton et al, 1996). Although much is known about the mechanisms by which peripheral GLP-1R activation engages these physiological responses, the relevant central GLP-1R populations and their projections, as well as the intracellular signaling cascades that mediate the food intake inhibitory effects of central GLP-1R-activation have received considerably less attention.…”

Mediterranean style diet is associated with low risk of new-onset diabetes after renal transplantation

“…A high intake of monounsaturated fatty acids benefits glycemic control, since it stimulates the secretion of glucagon-like peptide-1 (GLP-1), an antidiabetic hormone 42. GLP-1 activates the GLP-1 receptor in the pancreatic islets, which leads to an increase in secretion of insulin and inhibition of glucagon 43. Furthermore, GLP-1 plays a role in satiety 44…”

The role of the Wnt signaling pathway in incretin hormone production and function

“…In addition, GLP-1 as well as GIP increased insulin mRNA levels, possibly through stimulating insulin gene transcription and mRNA stability. GLP-1 inhibits glucagon secretion from α-cells and stimulates the secretion of somatostatin from δ-cells (D'Alessio et al, 1989; Komatsu et al, 1989). The stimulation of somatostatin secretion by GLP-1 could be directly mediated by its receptor on pancreatic islet δ-cells, while the inhibition of glucagon secretion could be indirectly mediated through the inhibition of somatostatin and the stimulation of insulin secretion.…”