Dynamic changes in {beta}-cell mass and pancreatic insulin during the evolution of nutrition-dependent diabetes in psammomys obesus: impact of glycemic control.

Abstract

Recent studies ascribe a major role to pancreatic beta-cell loss in type 2 diabetes. We investigated the dynamics of beta-cell mass during diabetes evolution in Psammomys obesus, a model for nutrition-dependent type 2 diabetes, focusing on the very early and the advanced stages of the disease. P. obesus fed a high-calorie diet for 26 days developed severe hyperglycemia, beta-cell degranulation, and markedly reduced pancreatic insulin content. Reducing calories for 7 days induced normoglycemia in 90% of the animals, restoring beta-cell granulation and insulin content. To dissociate effects of diet from blood glucose reduction, diabetic animals received phlorizin for 2 days, which normalized glycemia and increased the pancreatic insulin reserve to 50% of control, despite a calorie-rich diet. During diabetes progression, beta-cell mass decreased initially but recovered spontaneously to control levels, despite persistent hyperglycemia. Strikingly, however, beta-cell mass did not correlate with degree of hyperglycemia or pancreatic insulin content. We conclude that reduced insulin reserve is the main cause of diabetes progression, whereas irreversible beta-cell mass reduction is a late event in P. obesus. The rapid recovery of the pancreas by phlorizin-induced normoglycemia implies a causal relationship between hyperglycemia and islet dysfunction. Similar mechanisms could be operative during the evolution of type 2 diabetes in humans.

• Authors: Nurit Kaiser, Michal Yuli, Gökhan Uçkaya, Andrei I Oprescu, Marie-France Berthault, Catherine Kargar, Marc Y Donath, Erol Cerasi, Alain Ktorza
• Journal: Diabetes (Diabetes) Vol. 54 Issue 1 Pg. 138-45 (Jan 2005) ISSN: 0012-1797 [Print] United States
• PMID: 15616021 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin
• Phlorhizin

Topics

• Animals
• Diabetes Mellitus, Type 2 (pathology, physiopathology, therapy)
• Diet
• Diet, Diabetic
• Energy Metabolism
• Gerbillinae (anatomy & histology)
• Insulin (metabolism)
• Insulin Secretion
• Islets of Langerhans (anatomy & histology, metabolism, pathology)
• Kinetics
• Phlorhizin (therapeutic use)
• Time Factors