New "Exercise in a Petri Dish" Model Shows Protective Effect against Type 2 Diabetes-Related Insulin Resistance

For years, doctors have recommended exercise to help patients control their diabetes. But how exactly does exercise help? New research from the lab of John Kirwan, PhD, Department of Pathobiology, demonstrates for the first time that muscle contraction protects against insulin resistance at a cellular level.

Dr. Kirwan and others in the field have previously shown that exercise can protect against lipid-induced insulin resistance, a well-known risk factor for type 2 diabetes. Insulin resistant cells do not properly respond to insulin and therefore cannot easily absorb glucose into the cells for energy. As a result, the body needs to produce higher and higher levels of insulin. In lipid-induced insulin resistance, excessive fatty acids lead to poor insulin signaling and glucose uptake.

Exercise is a multi-faceted event that involves many systems, including the metabolic, cardiovascular and musculoskeletal systems. Rather than simulating all of these complex processes in cell culture, Dr. Kirwan and his team set out to determine whether muscle contraction alone would prove enough to alter insulin resistance.

The researchers simulated muscle contraction by exposing myotubes, or skeletal muscle fiber cells, to electrical pulse stimulation (EPS) and then measured how well the cells absorbed glucose when stimulated with insulin. The cells that received EPS absorbed over 80% more glucose than the non-stimulated cells. Even cells exposed to EPS and then challenged with a saturated lipid solution, which typically inhibits glucose uptake, absorbed 68% more glucose than control cells.

These findings—which validate Dr. Kirwan's and others' earlier ex vivo and in vitro findings about exercise, glucose uptake and insulin signaling—suggest this in vivo model may allow for higher throughput and help researchers uncover the cellular mechanisms of exercise and lipid metabolism. Additionally, with the knowledge that muscle contraction alone delivers these benefits, this work offers hope that physicians may one day be able to prescribe more targeted treatment and prevention therapies for type 2 diabetes.

This paper was published in the American Journal of Physiology—Cell Physiology.