Dynamic changes in {beta}-cell mass and pancreatic insulin during the evolution of nutrition-dependent diabetes in psammomys obesus: impact of glycemic control.
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.
Kaiser
Nurit
N
Endocrinology and Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, P.O. Box 12000, Jerusalem 91120, Israel. kaiser@md.huji.ac.il
Yuli
Michal
M
Uçkaya
Gökhan
G
Oprescu
Andrei I
AI
Berthault
Marie-France
MF
Kargar
Catherine
C
Donath
Marc Y
MY
Cerasi
Erol
E
Ktorza
Alain
A
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology* / Q000628:therapy; D004032:Diet; D003927:Diet, Diabetic; D004734:Energy Metabolism; D005849:Gerbillinae / Q000033:anatomy & histology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000033:anatomy & histology* / Q000378:metabolism / Q000473:pathology; D007700:Kinetics; D010695:Phlorhizin / Q000627:therapeutic use; D013997:Time Factors
D007328:Insulin; D010695:Phlorhizin