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 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 Paris, M. Articles by Ktorza, A. Search for Related Content PubMed PubMed Citation Articles by Paris, M. Articles by Ktorza, A.

Specific and Combined Effects of Insulin and Glucose on Functional Pancreatic ß-Cell Mass in Vivo in Adult Rats

Laboratoire de Physiopathologie de la Nutrition (M.P., C.B.-K., M.-F.B., A.K.), Centre National de la Recherche Scientifique, Unité Mixte de Recherche, 7059, Université Paris 7, 75251 Paris, France; and Cell Differentiation Group (L.B.), Diabetes Research Center, Free University of Brussels (VUB), Brussels 1050, Belgium

Address all correspondence and requests for reprints to: Maryline Paris, Laboratoire de Physiopathologie de la Nutrition, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7059, Université Paris 7, case 7126, 2 place Jussieu, 75251 Paris, France. E-mail: mparis{at}paris7.jussieu.fr.

We investigated the specific and associated effects of insulin and glucose on ß-cell growth and function in adult rats. By combining simultaneous infusion either of glucose and/or insulin or glucose and diazoxide, three groups of rats were constituted: hyperglycemic-hyperinsulinemic rats (high glucose–high insulin), hyperglycemic-euinsulinemic rats (high glucose), and euglycemic-hyperinsulinemic rats (high insulin). All the infusions lasted 48 h. Control rats were infused with 0.9% NaCl (saline controls). In all groups, ß-cell mass was significantly increased, compared with controls (by 70% in high glucose–high insulin rats, 65% in high glucose rats, and 50% in high insulin rats). The stimulation of neogenesis was suggested by the high number of islets budding from pancreatic ducts in high glucose–high insulin and high glucose rats and by the presence of numerous clusters of few ß-cells within the exocrine pancreas in high insulin rats. ß-Cell hypertrophy was observed only in high glucose–high insulin rats. The rate of ß-cell proliferation was similar to that of controls in high glucose–high insulin rats after a 48-h glucose infusion, dropped dramatically in high insulin rats, and dropped to a lesser extent in high glucose rats. In high glucose–high insulin and high glucose rats, ß-cell mass increase was related to a higher ß-cell responsiveness to glucose in vitro as measured by islet perifusion studies, whereas in high insulin rats, no significant enhancement of glucose induced insulin secretion could be noticed. The data show that glucose and insulin may have specific stimulating effects on ß-cell growth and function in vivo in adult rats independently of the influence they exert each other on their respective plasma concentration.

This article has been cited by other articles:

				T. L. Jetton, B. Everill, J. Lausier, V. Roskens, A. Habibovic, K. LaRock, A. Gokin, M. Peshavaria, and J. L. Leahy Enhanced {beta}-cell mass without increased proliferation following chronic mild glucose infusion Am J Physiol Endocrinol Metab, April 1, 2008; 294(4): E679 - E687. [Abstract] [Full Text] [PDF]

				S.-J. Kim, C. Nian, S. Widenmaier, and C. H. S. McIntosh Glucose-Dependent Insulinotropic Polypeptide-Mediated Up-Regulation of {beta}-Cell Antiapoptotic Bcl-2 Gene Expression Is Coordinated by Cyclic AMP (cAMP) Response Element Binding Protein (CREB) and cAMP-Responsive CREB Coactivator 2 Mol. Cell. Biol., March 1, 2008; 28(5): 1644 - 1656. [Abstract] [Full Text] [PDF]

				D. K. Hagman, M. G. Latour, S. K. Chakrabarti, G. Fontes, J. Amyot, C. Tremblay, M. Semache, J. A. Lausier, V. Roskens, R. G. Mirmira, et al. Cyclical and Alternating Infusions of Glucose and Intralipid in Rats Inhibit Insulin Gene Expression and Pdx-1 Binding in Islets Diabetes, February 1, 2008; 57(2): 424 - 431. [Abstract] [Full Text] [PDF]

				L. C. Alonso, T. Yokoe, P. Zhang, D. K. Scott, S. K. Kim, C. P. O'Donnell, and A. Garcia-Ocana Glucose Infusion in Mice: A New Model to Induce {beta}-Cell Replication Diabetes, July 1, 2007; 56(7): 1792 - 1801. [Abstract] [Full Text] [PDF]

				M. Acosta-Martinez and J. E. Levine Regulation of KATP channel subunit gene expression by hyperglycemia in the mediobasal hypothalamus of female rats Am J Physiol Endocrinol Metab, June 1, 2007; 292(6): E1801 - E1807. [Abstract] [Full Text] [PDF]

				O. Strobel, Y. Dor, A. Stirman, A. Trainor, C. Fernandez-del Castillo, A. L. Warshaw, and S. P. Thayer beta cell transdifferentiation does not contribute to preneoplastic/metaplastic ductal lesions of the pancreas by genetic lineage tracing in vivo PNAS, March 13, 2007; 104(11): 4419 - 4424. [Abstract] [Full Text] [PDF]

				Q. Huang, S. Bu, Y. Yu, Z. Guo, G. Ghatnekar, M. Bu, L. Yang, B. Lu, Z. Feng, S. Liu, et al. Diazoxide Prevents Diabetes through Inhibiting Pancreatic {beta}-Cells from Apoptosis via Bcl-2/Bax Rate and p38-{beta} Mitogen-Activated Protein Kinase Endocrinology, January 1, 2007; 148(1): 81 - 91. [Abstract] [Full Text] [PDF]

				G. Path, A. Opel, M. Gehlen, V. Rothhammer, X. Niu, C. Limbert, L. Romfeld, S. Hugl, A. Knoll, M. D. Brendel, et al. Glucose-dependent expansion of pancreatic beta-cells by the protein p8 in vitro and in vivo Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1168 - E1176. [Abstract] [Full Text] [PDF]

				G. Kwon, C. A. Marshall, H. Liu, K. L. Pappan, M. S. Remedi, and M. L. McDaniel Glucose-stimulated DNA Synthesis through Mammalian Target of Rapamycin (mTOR) Is Regulated by KATP Channels: EFFECTS ON CELL CYCLE PROGRESSION IN RODENT ISLETS J. Biol. Chem., February 10, 2006; 281(6): 3261 - 3267. [Abstract] [Full Text] [PDF]

				L. Bouwens and I. Rooman Regulation of Pancreatic Beta-Cell Mass Physiol Rev, October 1, 2005; 85(4): 1255 - 1270. [Abstract] [Full Text] [PDF]

				W. L. Suarez-Pinzon, J. R. T. Lakey, S. J. Brand, and A. Rabinovitch Combination Therapy with Epidermal Growth Factor and Gastrin Induces Neogenesis of Human Islet {beta}-Cells from Pancreatic Duct Cells and an Increase in Functional {beta}-Cell Mass J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3401 - 3409. [Abstract] [Full Text] [PDF]

				G Uckaya, P Delagrange, A Chavanieu, G Grassy, M-F Berthault, A Ktorza, E Cerasi, G Leibowitz, and N Kaiser Improvement of metabolic state in an animal model of nutrition-dependent type 2 diabetes following treatment with S 23521, a new glucagon-like peptide 1 (GLP-1) analogue J. Endocrinol., March 1, 2005; 184(3): 505 - 513. [Abstract] [Full Text] [PDF]

				N. Kaiser, M. Yuli, G. Uckaya, A. I. Oprescu, M.-F. Berthault, C. Kargar, M. Y. Donath, E. Cerasi, and A. Ktorza Dynamic Changes in {beta}-Cell Mass and Pancreatic Insulin During the Evolution of Nutrition-Dependent Diabetes in Psammomys obesus: Impact of Glycemic Control Diabetes, January 1, 2005; 54(1): 138 - 145. [Abstract] [Full Text] [PDF]

				M. I. Borelli, F. Francini, and J. J. Gagliardino Autocrine regulation of glucose metabolism in pancreatic islets Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E111 - E115. [Abstract] [Full Text]