flavin-adenine-dinucleotide and Diabetes-Mellitus--Type-1

Topics: Alloxan; Animals; Antigens, Surface; Cell Separation; Cells, Cultured; Cyclic AMP; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Flavin-Adenine Dinucleotide; Flow Cytometry; Glucagon; Glucose; Insulin; Insulin Secretion; Islets of Langerhans; Islets of Langerhans Transplantation; NADP; Somatostatin; Streptozocin

Topics: Apoptosis; Cell Separation; Cells, Cultured; Diabetes Mellitus, Type 1; fas Receptor; Flavin-Adenine Dinucleotide; Flow Cytometry; Humans; In Vitro Techniques; Interleukin-1; Islets of Langerhans; Light; Scattering, Radiation

In pancreatic islet extracts of rats with hereditary non-insulin-dependent diabetes mellitus (GK rats), the activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase, as measured by either a radioisotopic or colorimetric procedure, only represented 30 to 40% of that found in control rats. This decrease in enzymic activity was not attributable to any sizeable change in either islet DNA content or the relative contribution of insulin-producing beta cells to total islet mass. It contrasted with a normal activity of other mitochondrial dehydrogenases and hexokinase isoenzymes. It coincided, however, with an increased activity of glutamate-pyruvate transaminase, as already observed in adult rats injected with streptozotocin during the neonatal period. The decreased activity of islet FAD-linked glycerophosphate dehydrogenase also contrasted with an increased activity of the same enzyme in the liver of GK, as compared to control rats. In the light of these findings and recent metabolic data collected in intact islets of GK rats, it is proposed that a deficiency of beta-cell FAD-linked glycerophosphate dehydrogenase, the key enzyme of the glycerol phosphate shuttle, may represent a cause of inherited non-insulin-dependent diabetes.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Blood Glucose; Diabetes Mellitus, Type 1; Flavin-Adenine Dinucleotide; Glutamate Dehydrogenase; Glycerolphosphate Dehydrogenase; Hexokinase; Insulin; Islets of Langerhans; Isoenzymes; Ketoglutarate Dehydrogenase Complex; Kinetics; Liver; Mitochondria; Mitochondria, Liver; Rats; Rats, Mutant Strains; Rats, Wistar