exploring-mitochondrial-energy-metabolism-single-3d-microtissue

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

Three-dimensional (3D) cellular aggregates, termed spheroids, have become the forefront of in vitro cell culture in recent years. In contrast to culturing ...

University of Birmingham

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.

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

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.

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

J. P. Barlow

Mitochondrial Profiling Centre

University of Birmingham

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

J. P. Barlow

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University of Birmingham

Exploring Mitochondrial Energy Metabolism of Single 3D Microtissue Spheroids Using Extracellular Flux Analysis

Mitochondrial Profiling Centre