Evidence of enhancement of malate-aspartate shuttle activity in β cells of streptozotocin-induced non—insulin-dependent diabetic rats

Abstract

Glucose-induced insulin secretion is selectively impaired in β cells from animals with non—insulin-dependent diabetes mellitus (NIDDM). This study was performed to clarify whether the malate-aspartate shuttle among the glucose metabolic pathways is intact in β cells of NIDDM rats. The insulin secretory capacity of the islets and the KATP channel activity in single β cells were measured in control and NIDDM rats injected with streptozotocin (STZ) during the neonatal period, using a radioimmunoassay and patch-clamp technique. The increase of insulin secretion induced by 11.1 mmol/L glucose 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 increase in insulin secretion, but the difference between the 2 groups was indistinguishable. On the contrary, the increase of insulin secretion and the inhibition of KATP channel activity induced by aspartate, which preferentially 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 KATP channel activity. These findings show that malate-aspartate shuttle activity is potentiated in pancreatic β cells of NIDDM rats, suggesting the development of a compensatory mechanism for the reduced activity of the glycerol-phosphate shuttle in NIDDM.