Acceleration of the development of diabetes in obese diabetic (db/bd) miceby nicotinamide: A comparison with its antidiabetic effects in non-obese diabetic mice

Destruction of pancreatic beta cells has been implicted in the progression to hyperglycemia in type 1 diabetes. While there is evidence of beta -cell loss in type 2 diabetes, its contribution to the development of the diabeti c state is undecided. Nicotinamide has defensive effects against toxic insu lts to the pancreatic islets and confers protection in both human and anima l models of type 1 diabetes, but its effects on type 2 diabetes are less we ll documented. This report describes a comparison of the outcome of chronic oral administration of nicotinamide on the development of diabetes in obes e diabetic (db/db) and non-obese diabetic (NOD) mice models of type 2 and t ype 1 diabetes, respectively. Nicotinamide was administered in the diet (5 g/kg diet) for 12 (db/db) or 24 (NOD) weeks. Over the 1:2 weeks of the stud y, control diabetic (db/db) mice became progressively more hyperglycemic an d glycosuric, while serum and pancreatic insulin levels decreased compared with those on day 0. In mice treated with nicotinamide, there was a pronoun ced acceleration in the development of hyperglycemia and glycosuria, as wel l as a decrease in pancreatic insulin levels, compared with time-matched co ntrols. In addition, the morphology of the pancreatic islets of nicotinamid e-treated diabetic (db/db) mice showed an enhanced islet disorganization. B y comparison, in NOD mice, nicotinamide prevented the decline in serum and pancreatic insulin levels and maintained normal islet architecture and insu lin content. Our data shows that in contrast to its preventative effects on the development of autoimmune diabetes in NOD mice, chronic nicotinamide a dministration to obese diabetic (db/db) mice markedly accelerated the progr ession of diabetes. The results of our study caution against the use of nic otinamide in insulin-resistant states, such as type 2 diabetes. Copyright ( C) 2000 by W.B. Saunders Company.