Evidence of enhancement of malate-aspartate shuttle activity in beta cellsof streptozotocin-induced non-insulin-dependent diabetic rats

Glucose-induced insulin secretion is selectively impaired in beta cells fro m animals with non-insulin-dependent diabetes mellitus (NIDDM). This study was performed to clarify whether the malate-aspartate shuttle among the glu cose metabolic pathways is intact in beta cells of NIDDM rats. The insulin secretory capacity of the islets and the K-ATP channel activity in single b eta cells were measured in control and NIDDM rats injected with streptozoto cin (STZ) during the neonatal period, using a radioimmunoassay and patch-cl amp technique. The increase of insulin secretion induced by 11.1 mmol/L glu cose or 10 mmol/L dihydroxyacetone (DHA) was significantly reduced in NIDDM islets, suggesting an impaired glycerol-phosphate shuttle. The application of glyceraldehyde (10 mmol/L) in NIDDM or control islets elicited an incre ase in insulin secretion, but the difference between the 2 groups was indis tinguishable. On the contrary, the increase of insulin secretion and the in hibition of K-ATP channel activity induced by aspartate, which preferential ly participates in the malate-aspartate shuttle, were significantly greater in NIDDM versus the control. However, intracellularly applied aspartate in the inside-out mode did not inhibit K-ATP channel activity. These findings show that malate-aspartate shuttle activity is potentiated in pancreatic b eta cells of NIDDM rats, suggesting the development of a compensatory mecha nism for the reduced activity of the glycerol-phosphate shuttle in NIDDM. C opyright (C) 2000 by W.B. Saunders Company.