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Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Taylor, Ashley, Irwin, Nigel, McKillop, Aine, Patterson, Steven, Flatt, Peter and Gault, Victor (2010) Evaluation of the degradation and metabolic effects of the gut peptide xenin on insulin secretion, glycaemic control and satiety. JOURNAL OF ENDOCRINOLOGY, 207 (1). pp. 87-93. [Journal article]

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DOI: 10.1677/JOE-10-0085

Abstract

Recently, glucagon-like peptide 1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP) have received much attention regarding possible roles in aetiology and treatment of type 2 diabetes. However, peptides co-secreted from the same enteroendocrine cells are less well studied. The present investigation was designed to characterise the in vitro and in vivo effects of xenin, a peptide co-secreted with GIP from intestinal K-cells. We examined the enzymatic stability, insulin-releasing activity and associated cAMP production capability of xenin in vitro. In addition, the effects of xenin on satiety, glucose homoeostasis and insulin secretion were examined in vivo. Xenin was time dependently degraded (t(1/2) = 162+/-6 min) in plasma in vitro. In clonal BRIN-BD11 cells, xenin stimulated insulin secretion at 5.6 mM(P<0.05) and 16.7 mM (P<0.05 to P<0.001) glucose levels compared to respective controls. Xenin also exerted an additive effect on GIP, GLP1 and neurotensin-mediated insulin secretion. In clonal beta-cells, xenin did not stimulate cellular cAMP production, alter membrane potential or elevate intra-cellular Ca2+. In normal mice, xenin exhibited a short-acting (P<0.01) satiety effect at high dosage (500 nmol/kg). In overnight fasted mice, acute injection of xenin enhanced glucose-lowering and elevated insulin secretion when injected concomitantly or 30 min before glucose. These effects were not observed when xenin was administered 60 min before the glucose challenge, reflecting the short half-life of the native peptide in vivo. Overall, these data demonstrate that xenin may have significant metabolic effects on glucose control, which merit further study. Journal of Endocrinology (2010) 207, 87-93

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Faculty of Life and Health Sciences > School of Pharmacy and Pharmaceutical Science
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Diabetes
ID Code:16592
Deposited By:Dr Nigel Irwin
Deposited On:08 Dec 2010 11:57
Last Modified:19 Nov 2012 15:48

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