Effect of long-term insulin treatment on plasma and cardiac adiponectin levels in streptozotocin-induced diabetic mice

AIM:To investigate the time-course change of plasma and cardiac adiponectin levels in streptozotocin (STZ)-induced diabetic mice, to determine the effect of insulin treatment on plasma and cardiac adiponectin levels and to discuss the possible mechanism of cardiac adiponectin in the protection against myocardial ischemia/reperfusion injury. METHODS: Seventy-two male mice were randomly assigned to control, type 1 diabetes and insulin treatment groups. Adiponectin levels in plasma and cardiac tissues were longitudinally detected at days 1, 7, and 14 after STZ-induced diabetes was confirmed through ELISA and qRT-PCR, respectively. To examine the changes of cardiac-derived adiponectin levels, hearts were isolated and perfused in a Langendorff preparation and then stained by TUNEL. RESULTS: Compared with control mice, plasma adiponectin level in type 1 diabetic mice increased at day 7 but decreased at day 14 ［D7: (5.23±1.05) mg/L vs. (3.45±0.51) mg/L, P<0.01］. Adiponectin mRNA level lowered gradually ［D7: (0.50±0.19) vs.(1.76±0.26), P<0.05］; ［D14: (0.10±0.05) vs.(1.77±0.41), P<0.01］. Compared with type 1 diabetic mice, plasma adiponectin level in insulin-treated mice was elevated ［D14: (3.61±0.71) vs. (2.16±0.49), P<0.05］ and adiponectin mRNA levels in cardiomyocytes were also elevated ［D7: (1.41±0.19) vs.(0.50±0.19), P<0.05］; ［D14: (0.80±0.17) vs.(0.10±0.05), P<0.05］. After ischemia/reperfusion, cardiac infarct size and cardiomyocyte apoptosis in type 1 diabetic mice markedly increased when compared with control mice (P<0.01). Long-term insulin treatment decreased infarct sizes and cardiomyocyte apoptosis in hearts of type 1 diabetic mice (P<0.01). Compound C, an inhibitor of adiponectin downstream signaling molecule AMPK, partially attenuated the effect of long-term insulin treatment (P<0.01). CONCLUSION: Plasma adiponectin levels in type 1 diabetic mice show a bidirectional change throughout the course of the disease. In cardiac tissues, local adiponectin level gradually decreases. Long-term insulin treatment may increase both plasma and local cardiac adiponectin levels. Increase of cardiac adiponectin may increase the tolerance of cardiomyocytes against ischemia/reperfusion injury.