Abstract
Exercise improves insulin secretion by pancreatic beta cells (β-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 β-cell crosstalk. Evidence to support a role of IL-6 in regulating the health and function of β-cells is currently inconsistent and studies investigating the role of IL-6 on the function of β-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 β-cells exposed to type 2 diabetic-like conditions. Using insulin-secreting INS-1 832/3 cells as an experimental β-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 ± palmitate or IL-1β. 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 β-cell function is unlikely to be driven by muscle-derived IL-6.
Highlights
The pathophysiology of type 2 diabetes (T2D) is incompletely understood, but it is generally accepted that hyperglycemia occurs only when insulin resistance is combined with β-cell dysfunction [1]
Exposure of INS-1 832/3 cells to increasing concentrations of IL-6 (0–10,000 pg/mL) has no significant pg/mL, IL-6 tends to lower Glucose-Stimulated Insulin Secretion (GSIS), which appears to be a result of suppressed insulin release by INS-1 effect on glucose-stimulated insulin secretion (GSIS) (Figure 1A)
Basal insulin secretion is not significantly affected by concentration that better reflects what is released into circulation following an acute bout of exercise increasing IL-6 (Figure 1B)
Summary
The pathophysiology of type 2 diabetes (T2D) is incompletely understood, but it is generally accepted that hyperglycemia occurs only when insulin resistance is combined with β-cell dysfunction [1]. Finding new therapies targeted at improving β-cell function is key to restoring normal blood glucose homeostasis in patients with T2D. Glucoregulatory benefits of exercise have been attributed to enhanced insulin sensitivity of peripheral tissues [5] and to improved β-cell function [6,7]. Active compounds released during exercise likely contribute to the protective effects of exercise in patients with T2D [10,11]. As many of these compounds are released by skeletal muscle [12], it is currently thought that muscle contraction mediates interorgan crosstalk with distant tissues, including
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