Psammomys obesus, a model for environment-gene interactions in type 2 diabetes.
Type 2 diabetes is characterized by insulin resistance and progressive beta-cell failure. Deficient insulin secretion, with increased proportions of insulin precursor molecules, is a common feature of type 2 diabetes; this could result from inappropriate beta-cell function and/or reduced beta-cell mass. Most studies using tissues from diabetic patients are retrospective, providing only limited information on the relative contribution of beta-cell dysfunction versus decreased beta-cell mass to the "beta-cell failure" of type 2 diabetes. The gerbil Psammomys obesus is a good model to address questions related to the role of insulin resistance and beta-cell failure in nutritionally induced diabetes. Upon a change from its natural low-calorie diet to the calorie-rich laboratory food, P. obesus develops moderate obesity associated with postprandial hyperglycemia. Continued dietary load, superimposed on its innate insulin resistance, results in depletion of pancreatic insulin stores, with increased proportions of insulin precursor molecules in the pancreas and the blood. Inadequate response of the preproinsulin gene to the increased insulin needs is an important cause of diabetes progression. Changes in beta-cell mass do not correlate with pancreatic insulin stores and are unlikely to play a role in disease initiation and progression. The major culprit is the inappropriate insulin production with depletion of insulin stores as a consequence. Similar mechanisms could operate during the evolution of type 2 diabetes in humans.
Kaiser
Nurit
N
Endocrinology and Metabolism Service, Department of Internal Medicine, Hebrew University-Hadassah Medical Center, Jerusalem, Israel. kaiser@md.huji.ac.il
Nesher
Rafael
R
Donath
Marc Y
MY
Fraenkel
Merav
M
Behar
Vered
V
Magnan
Christophe
C
Ktorza
Alain
A
Cerasi
Erol
E
Leibowitz
Gil
G
D000821:Animal Feed; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D004195:Disease Models, Animal; D004777:Environment; D005849:Gerbillinae; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism
D007328:Insulin