IJMS, Vol. 19, Pages 1924: Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions
International Journal of Molecular Sciences doi: 10.3390/ijms19071924
Thomas P. J. Solomon
Exercise improves insulin secretion by pancreatic beta cells (&beta;-cells) in patients with type 2 diabetes, but molecular mechanisms of this effect are yet to be determined. Given that contracting skeletal muscle causes a spike in circulating interleukin-6 (IL-6) levels during exercise, muscle-derived IL-6 is a possible endocrine signal associated with skeletal muscle to &beta;-cell crosstalk. Evidence to support a role of IL-6 in regulating the health and function of &beta;-cells is currently inconsistent and studies investigating the role of IL-6 on the function of &beta;-cells exposed to type 2 diabetic-like conditions are limited and often confounded by supraphysiological IL-6 concentrations. The purpose of this study is to explore the extent by which an exercise-relevant concentration of IL-6 influences the function of pancreatic &beta;-cells exposed to type 2 diabetic-like conditions. Using insulin-secreting INS-1 832/3 cells as an experimental &beta;-cell model, we show that 1-h IL-6 (10 pg/mL) has no effect on insulin secretion under normal conditions and does not restore the loss of insulin secretion caused by elevated glucose &plusmn; palmitate or IL-1&beta;. Moreover, treatment of INS-1 832/3 cells to medium collected from C2C12 myotubes conditioned with electrical pulse stimulation does not alter insulin secretion despite significant increases in IL-6. Since insulin secretory defects caused by diabetic-like conditions are neither improved nor worsened by exposure to physiological IL-6 levels, we conclude that the beneficial effect of exercise on &beta;-cell function is unlikely to be driven by muscle-derived IL-6.