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Journal of Diabetes Research
Volume 2015 (2015), Article ID 326359, 7 pages
http://dx.doi.org/10.1155/2015/326359
Research Article

Effects of High Glucose Levels and Glycated Serum on GIP Responsiveness in the Pancreatic Beta Cell Line HIT-T15

1Department of Internal Medicine, University of Genoa, Viale Benedetto XV, 16143 Genoa, Italy
2Division of Cardiology, Department of Medicine, Geneva University Hospitals, Faculty of Medicine, Foundation for Medical Researches, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland
3Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, 4 Rue Gabrielle-Perret-Gentil, 1205 Geneva, Switzerland

Received 10 December 2014; Accepted 17 June 2015

Academic Editor: Ike S. Okosun

Copyright © 2015 Alessandra Puddu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Glucose-dependent insulinotropic peptide (GIP) is an incretin hormone produced in the gastrointestinal tract that stimulates glucose dependent insulin secretion. Impaired incretin response has been documented in diabetic patients and was mainly related to the inability of the pancreatic beta cells to secrete insulin in response to GIP. Advanced Glycation End Products (AGEs) have been shown to play an important role in pancreatic beta cell dysfunction. The aim of this study is to investigate whether the exposure to AGEs can induce GIP resistance in the pancreatic beta cell line HIT-T15. Cells were cultured for 5 days in low (CTR) or high glucose (HG) concentration in the presence of AGEs (GS) to evaluate the expression of GIP receptor (GIPR), the intracellular signaling activated by GIP, and secretion of insulin in response to GIP. The results showed that incubation with GS alone altered intracellular GIP signaling and decreased insulin secretion as compared to CTR. GS in combination with HG reduced the expression of GIPR and PI3K and abrogated GIP-induced AKT phosphorylation and GIP-stimulated insulin secretion. In conclusion, we showed that treatment with GS is associated with the loss of the insulinotropic effect of GIP in hyperglycemic conditions.