Conditioned media from contracting skeletal muscle potentiates insulin secretion and enhances mitochondrial energy metabolism of pancreatic beta-cells

AIMS/HYPOTHESIS: In this study, we aimed to examine real-time effects of molecules released by contracting skeletal muscle on the insulin secretory function of β-cells using a novel perifusion platform. We hypothesised that media conditioned by contracting skeletal muscle will influence insulin secretion and mitochondrial energy metabolism in β-cells under normal and type-2 diabetic conditions.

METHODS: INS-1 832/3 pseudoislets were perifused with media from C2C12 myotubes treated with or without electrical pulse stimulation (EPS; 40 V, 1.0 Hz, 2 ms). Insulin secretory function of pseudoislets was measured before, during, and after EPS to simulate pre-, during-, and post-exercise like effects. Additional experiments were completed in INS-1 832/3 cells under "healthy" and "diabetic-like" conditions as well as human pancreatic islets isolated from nondiabetic and type 2 diabetic donors.

RESULTS: Insulin secretion increased significantly (P < 0.05) by pseudoislets when perifused with media from myotubes treated with but not without EPS. Conditioned media from EPS-treated myotubes also potentiated insulin secretion from INS-1 832/3 cell monolayers in the presence (P < 0.05) and absence of palmitate (P < 0.001) and in nondiabetic (P < 0.01) and type-2 diabetic (P = 0.06) isolated human islets. Pre-treatment of INS-1 832/3 cells to 24-hour high glucose ± palmitate dampened this effect. Moreover, conditioned media from myotubes treated with EPS significantly increased mitochondrial respiratory activity of INS-1 832/3 cells.

CONCLUSION/INTERPRETATION: Conditioned media from myotubes treated with EPS potentiates acute insulin release from normal cultured β-cells, nondiabetic islets and Type-2 diabetic islets and is associated with enhanced mitochondrial substrate oxidation.