This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hostens, K. Articles by Pipeleers, D. Search for Related Content PubMed PubMed Citation Articles by Hostens, K. Articles by Pipeleers, D. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB (L)-ARGININE GLUCOSE

Prolonged Exposure of Human ß-Cells to High Glucose Increases Their Release of Proinsulin during Acute Stimulation with Glucose or Arginine¹

Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium

Address all correspondence and requests for reprints to: Dr. D. Pipeleers, Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. E-mail: dpip{at}mebo.vub.ac.be

The disproportionate hyperproinsulinemia in type 2 diabetes has been attributed to either a primary ß-cell defect or a secondary dysregulation of ß cells under sustained hyperglycemia. This study examines the effect of a 10- to 13-day exposure to 20 mmol/L glucose on subsequent proinsulin and insulin release by human islets isolated from nondiabetic donors. Compared to control preparations kept at 6 mmol/L glucose, the high glucose cultured ß-cells released more proinsulin and less insulin during perifusion at 5, 10, or 20 mmol/L glucose. The lower amounts of secreted insulin resulted from a marked reduction in cellular insulin content (5-fold lower than in controls). The higher amount of secreted proinsulin is attributed to the sustained state of cellular activation that is known to occur after prolonged exposure to high glucose levels. This activated state of the ß-cell population is also held responsible for its higher secretory responsiveness to 5 mmol/L arginine at a submaximal (5 mmol/L) glucose concentration (8-fold higher proinsulin levels than in the control population). It results, together with the reduction in cellular insulin content, in 7- to 10-fold higher proinsulin over insulin ratios in the medium; at 5 mmol/L glucose, this extracellular ratio is similar to that in the cells. These data add direct support to the view that a disproportionate hyperproinsulinemia can result from a sustained activation of human ß-cells after prolonged exposure to elevated glucose levels.

This article has been cited by other articles:

				E. Tweedie, I. Artner, L. Crawford, G. Poffenberger, B. Thorens, R. Stein, A. C. Powers, and M. Gannon Maintenance of Hepatic Nuclear Factor 6 in Postnatal Islets Impairs Terminal Differentiation and Function of {beta}-Cells Diabetes, December 1, 2006; 55(12): 3264 - 3270. [Abstract] [Full Text] [PDF]

				G. Harb and G. S Korbutt Effect of prolonged in vitro exposure to high glucose on neonatal porcine pancreatic islets. J. Endocrinol., October 1, 2006; 191(1): 37 - 44. [Abstract] [Full Text] [PDF]

				D. Chin, S. E. Oberfield, M. E. Silfen, D. J. McMahon, A. M. Manibo, D. Accili, and L. S. Levine Proinsulin in Girls: Relationship to Obesity, Hyperinsulinemia, and Puberty J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4673 - 4677. [Abstract] [Full Text] [PDF]