HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lupi, R. Articles by Marchetti, P. Search for Related Content PubMed PubMed Citation Articles by Lupi, R. Articles by Marchetti, P. Social Bookmarking                What's this?

Lipotoxicity in Human Pancreatic Islets and the Protective Effect of Metformin

¹ Department of Endocrinology and Metabolism, Metabolic Unit, University of Pisa, Pisa, Italy
² Department of General Pathology, University of Pisa, Pisa, Italy
³ Deparment of Endocrinology, University of Catania, Catania, Italy
⁴ Department of Oncology, University of Pisa, Pisa, Italy

Human pancreatic islets from eight donors were incubated for 48 h in the presence of 2.0 mmol/l free fatty acid (FFA) (oleate to palmitate, 2 to 1). Insulin secretion was then assessed in response to glucose (16.7 mmol/l), arginine (20 mmol/l), and glyburide (200 µmol/l) during static incubation or by perifusion. Glucose oxidation and utilization and intra-islet triglyceride content were measured. The effect of metformin (2.4 µg/ml) was studied because it protects rat islets from lipotoxicity. Glucose-stimulated but not arginine- or glyburide-stimulated insulin release was significantly lower from FFA-exposed islets. Impairment of insulin secretion after exposure to FFAs was mainly accounted for by defective early-phase release. In control islets, increasing glucose concentration was associated with an increase in glucose utilization and oxidation. FFA incubation reduced both glucose utilization and oxidation at maximal glucose concentration. Islet triglyceride content increased significantly after FFA exposure. Addition of metformin to high-FFA media prevented impairment in glucose-mediated insulin release, decline of first-phase insulin secretion, and reduction of glucose utilization and oxidation without significantly affecting islet triglyceride accumulation. These results show that lipotoxicity in human islets is characterized by selective loss of glucose responsiveness and impaired glucose metabolism, with a clear defect in early-phase insulin release. Metformin prevents these deleterious effects, supporting a direct protective action on human ß-cells.

CiteULike

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				H. K Nyblom, E. Sargsyan, and P. Bergsten AMP-activated protein kinase agonist dose dependently improves function and reduces apoptosis in glucotoxic {beta}-cells without changing triglyceride levels J. Mol. Endocrinol., September 1, 2008; 41(3): 187 - 194. [Abstract] [Full Text] [PDF]

				G. Bikopoulos, A. da Silva Pimenta, S. C Lee, J. R Lakey, S. D Der, C. B Chan, R. B. Ceddia, M. B Wheeler, and M. Rozakis-Adcock Ex vivo transcriptional profiling of human pancreatic islets following chronic exposure to monounsaturated fatty acids J. Endocrinol., March 1, 2008; 196(3): 455 - 464. [Abstract] [Full Text] [PDF]

				Y. Zhang, M. Xu, S. Zhang, L. Yan, C. Yang, W. Lu, Y. Li, and H. Cheng The role of G protein-coupled receptor 40 in lipoapoptosis in mouse {beta}-cell line NIT-1 J. Mol. Endocrinol., June 1, 2007; 38(6): 651 - 661. [Abstract] [Full Text] [PDF]

				L. Guiducci, T. Gronroos, M. J. Jarvisalo, J. Kiss, A. Viljanen, A. G. Naum, T. Viljanen, T. Savunen, J. Knuuti, E. Ferrannini, et al. Biodistribution of the Fatty Acid Analogue 18F-FTHA: Plasma and Tissue Partitioning Between Lipid Pools During Fasting and Hyperinsulinemia J. Nucl. Med., March 1, 2007; 48(3): 455 - 462. [Abstract] [Full Text] [PDF]

				S. Del Guerra, R. Lupi, L. Marselli, M. Masini, M. Bugliani, S. Sbrana, S. Torri, M. Pollera, U. Boggi, F. Mosca, et al. Functional and Molecular Defects of Pancreatic Islets in Human Type 2 Diabetes Diabetes, March 1, 2005; 54(3): 727 - 735. [Abstract] [Full Text] [PDF]

				E. Mannucci and C. M. Rotella Response to Hinke et al. Diabetes Care, August 1, 2002; 25(8): 1491 - 1492. [Full Text]

				L. S. Hermann and N. Wiernsperger Impaired glucose tolerance and metformin: clinical and mechanistic aspects The British Journal of Diabetes & Vascular Disease, May 1, 2002; 2(3): 177 - 183. [Abstract] [PDF]