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Matrix member key to insulin resistance

Jun. 6, 2013, 8:00 AM

Insulin in vials

Insulin resistance – the failure of cells to respond to the hormone insulin – is a risk factor for many metabolic disorders, including type 2 diabetes and cardiovascular diseases. Increased levels of extracellular matrix (ECM) components have been associated with insulin resistance.

Li Kang, Ph.D., research instructor in Molecular Physiology and Biophysics, and colleagues have now explored the role of the ECM constituent hyaluronan in insulin-resistant skeletal muscle. They found increased levels of muscle hyaluronan in high-fat diet induced obese (DIO) mice – a model of insulin resistance. Treatment of the DIO mice with a compound that degrades hyaluronan (called PEGPH20) dose-dependently reduced hyaluronan levels in muscle, improved muscle vascularity and reversed insulin resistance in muscle and in liver.

The findings, reported in the June issue of the journal Diabetes, demonstrate that hyaluronan plays a role in the pathogenesis of insulin resistance and that it may be a valuable target for treatment. Identifying cost-effective therapies for insulin resistance is important given the high prevalence and consequences of the condition.

This research was supported by grants from the National Institutes of Health (DK054902, DK059637, DK020593) and in part by a grant from Halozyme Therapeutics, Inc.

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