Send to

Choose Destination
Diabetes. 2013 Dec;62(12):4144-53. doi: 10.2337/db12-1657. Epub 2013 Apr 29.

Pancreatic islet vasculature adapts to insulin resistance through dilation and not angiogenesis.

Author information

Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.


Pancreatic islets adapt to insulin resistance through a complex set of changes, including β-cell hyperplasia and hypertrophy. To determine if islet vascularization changes in response to insulin resistance, we investigated three independent models of insulin resistance: ob/ob, GLUT4(+/-), and mice with high-fat diet-induced obesity. Intravital blood vessel labeling and immunocytochemistry revealed a vascular plasticity in which islet vessel area was significantly increased, but intraislet vessel density was decreased as the result of insulin resistance. These vascular changes were independent of islet size and were only observed within the β-cell core but not in the islet periphery. Intraislet endothelial cell fenestration, proliferation, and islet angiogenic factor/receptor expression were unchanged in insulin-resistant compared with control mice, indicating that islet capillary expansion is mediated by dilation of preexisting vessels and not by angiogenesis. We propose that the islet capillary dilation is modulated by endothelial nitric oxide synthase via complementary signals derived from β-cells, parasympathetic nerves, and increased islet blood flow. These compensatory changes in islet vascularization may influence whether β-cells can adequately respond to insulin resistance and prevent the development of diabetes.

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substance, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center