Study May Point to New Ways to Reverse Insulin Resistance


Source: Vanderbilt University

Summary: Researchers have discovered how insulin crosses the capillary endothelium to exit blood vessels and stimulate skeletal muscle cells, a major finding that may lead to new ways to reverse insulin resistance.


Insulin resistance (IR) is a condition in which cells fail to respond normally to the hormone insulin (produced by the pancreas). Digestion of carbohydrates in the diet releases glucose into the bloodstream. In response to this glucose, the body produces insulin. One of insulin’s key functions is to stimulate glucose uptake by muscle, where it is stored or used as fuel. To stimulate glucose uptake, insulin must cross the endothelial barrier into muscle tissue. Impaired delivery of insulin into tissue is a key feature of insulin resistance and type 2 diabetes. Researchers from the Vanderbilt University have discovered how insulin crosses the capillary endothelium to exit blood vessels and stimulate skeletal muscle cells, a major finding that may lead to new ways to reverse insulin resistance. The study findings were published in the Journal of Clinical Investigation.

Cells fail respond to insulin

David Wasserman, PhD, left, and Ian Williams, a graduate student in Wasserman’s lab, have made an important discovery that could lead to new ways to reverse insulin resistance, a hallmark of type 2 diabetes. Credit: Susan Urmy

Their discovery was made possible by the development of a novel microscopy technique which allowed measurement of insulin movement across the endothelial wall of skeletal muscle capillaries in the mouse. The researchers showed that insulin moves across the endothelium by fluid-phase transport by using a quantitative intravital fluorescence microscopy technique that was developed by them and combined with mathematical modeling. A better understanding of the variables controlling insulin movement across the endothelial wall could lead to improved strategies for reversing insulin resistance, including the development of small molecules that enhance insulin delivery or novel insulin analogs that can access muscle more easily. The fluorescence microscopy technique developed for these studies can be applied to other drugs and hormones to study molecular access to a range of tissues.

Prof. David Wasserman said, “The muscle capillary wall is a formidable barrier to insulin’s action on muscles”, “It is the rate-limiting step for muscle insulin action and a potential site of regulation” and further added, “Defining how insulin leaves the capillary is essential to understanding and treating insulin resistance.”


More Information: Ian M. Williams et al, “Insulin exits skeletal muscle capillaries by fluid-phase transport”, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI94053 


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