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 pancreatic beta cells was observed by morphometric analysis. In diabetic islets, as compared to control islets, insulin release was decreased in response to high glucose but not to other stimuli, and total glucose oxidation and utilization were unchanged or slightly reduced. The extent of metabolic and functional 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 dehydrogenase (mGDH), the key enzyme of the glycerophosphate shuttle. Interestingly, in diabetic islets, as recently reported for mGDH-deficient transgenic mice, definite functional alterations (mainly in response to D-glyceraldehyde) were only obtained upon pharmacological blockade of the second shuttle (i.e. malate-aspartate) responsible for mitochondrial transfer of reducing 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 intervention of adaptive mechanisms, yet prone to failure in challenging situations.
Novelli
M
M
Dipartimento di Patologia Sperimentale, Tecnologie Biomediche, Infettivologia e Epidemiologia, University of Pisa, Via Roma 55, Scuola Medica 56126, Pisa, Italy.
Fabregat
M E
ME
Fernandez-Alvarez
J
J
Gomis
R
R
Masiello
P
P
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000209:etiology / Q000473:pathology*; D004195:Disease Models, Animal; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D009536:Niacinamide; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin
D007328:Insulin; D000625:Aminooxyacetic Acid; D009536:Niacinamide; D013311:Streptozocin; D005993:Glycerolphosphate Dehydrogenase; D005947:Glucose