Metabolic and functional studies on isolated islets in a new rat model of type 2 diabetes

In a new experimental type 2 diabetic syndrome, a 40% reduction of pancreat ic beta cells was observed by morphometric analysis. In diabetic islets, as compared to control islets, insulin release was decreased in response to h igh glucose but not to other stimuli, and total glucose oxidation and utili zation were unchanged or slightly reduced. The extent of metabolic and func tional impairment appeared proportional to the beta -cell loss. However, a substantial decrease was found in protein level and activity (by 77 and 60% , respectively, versus controls) of mitochondrial FAD-glycerophosphate dehy drogenase (mGDH), the key enzyme of the glycerophosphate shuttle. Interesti ngly, in diabetic islets, as recently reported for mGDH-deficient transgeni c mice, definite functional alterations (mainly in response to D-glyceralde hyde) were only obtained upon pharmacological blockade of the second shuttl e (i.e. malate-aspartate) responsible for mitochondrial transfer of reducin g equivalents. In conclusion, in this diabetes model with reduction of beta -cell mass, the islets, despite decreased mGDH amount and activity, appear metabolically and functionally active in vitro, likely through the interve ntion of adaptive mechanisms, yet prone to failure in challenging situation s. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.