Insulin modulates ischemia-induced endothelial progenitor cell mobilization and neovascularization in diabetic mice

Li Dong, Lina Kang, Liang Ding, Qin Chen, Jian Bai, Rong Gu, Lixin Li, Biao Xu
Microvascular Research 2011, 82 (3): 227-36
Decreased levels of circulating endothelial progenitor cells (EPCs) predict increased risk of cardiovascular events in diabetic patients. Insulin treatment exerts important cardiovascular protection. Whether and how insulin participates in the EPC regulation of postnatal neovascularization are currently unclear. We employed a mouse hindlimb ischemia model to study EPC mobilization in non-diabetic and streptozotocin-induced diabetic mice. Insulin was administered to diabetic animals postoperatively. To determine the role of EPCs contributing to postnatal vasculogenesis, we used bone marrow-transplanted mice whose bone marrow cells selectively expressed enhanced green fluorescent protein (EGFP). Insulin treatment improved EPC mobilization into peripheral blood, accelerated transcutaneous oxygen pressure restoration and increased capillary density in the ischemic limb associated with partial incorporation of EGFP-positive cells into the capillaries. Insulin treatment restored ischemia-induced release of stromal-derived growth factor 1α and vascular endothelial growth factor (VEGF), and consequently enhanced the activity of Akt and endothelial nitric oxide synthase (eNOS) as well as matrix metalloproteinase-9 in bone marrow. Insulin also augmented tissue-level activation of VEGF/Akt/eNOS pathway. However, all such effects of insulin were completely blocked by combined treatment with a NOS inhibitor. Our data suggested that insulin treatment improved ischemia-induced EPC mobilization and contributed to compensatory neovascularization in diabetic mice through a VEGF/eNOS-related pathway.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"