Obesity increases the risk of type 2 diabetes and cardiovascular disease through defective cellular responses to insulin. Insulin resistance is a growing public health concern, but the development of effective interventions has been limited by an incomplete understanding of the underlying molecular mechanisms.

Researchers developed a cellular model of insulin resistance in skeletal muscle tissue, which is affected during early stages of type 2 diabetes.

The authors obtained skin cells from four healthy individuals and four patients with Donohue syndrome, which causes insulin resistance through mutations in the insulin receptor. Next, the authors genetically reprogrammed the skin cells into induced pluripotent stem (iPS) cells, which are capable of turning into multiple cell types.

Upon exposure to a specific combination of chemicals, the iPS cells transformed into skeletal muscle fibers known as myotubes. Compared with myotubes derived from healthy individuals, the patient-derived myotubes showed not only a 90% reduction in levels of the insulin receptor but also impaired insulin signaling.

Moreover, insulin treatment failed to trigger an increase in the activity of genes that regulate metabolism and growth in patient-derived myotubes.

According to the authors, the iPS model of insulin resistance could help identify new therapies for type 2 diabetes and related diseases. 

http://www.pnas.org/content/early/2016/01/25/1525665113