Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions

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@article{b39f3f5e499f4ad999e4b51645295a4b,
title = "Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions",
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.",
keywords = "pancreatic beta cell dysfunction, insulin secretion, interleukin-6, type 2 diabetes, exercise, skeletal muscle, electrical pulse stimulation, organ crosstalk",
author = "Jonathan Barlow and Steven Carter and Thomas Solomon",
year = "2018",
month = jun,
day = "30",
doi = "10.3390/ijms19071924",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI",
number = "7",

}

RIS

TY - JOUR

T1 - Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions

AU - Barlow, Jonathan

AU - Carter, Steven

AU - Solomon, Thomas

PY - 2018/6/30

Y1 - 2018/6/30

N2 - 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.

AB - 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.

KW - pancreatic beta cell dysfunction

KW - insulin secretion

KW - interleukin-6

KW - type 2 diabetes

KW - exercise

KW - skeletal muscle

KW - electrical pulse stimulation

KW - organ crosstalk

U2 - 10.3390/ijms19071924

DO - 10.3390/ijms19071924

M3 - Article

C2 - 29966345

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 7

M1 - 1924

ER -