Premium
Role of insulin and hyperglycemia in angiogenic sprouting and microvessel survival
Author(s) -
Krishnan Laxminarayanan,
Chang Carlos C,
Williams Stuart K,
Hoying James B
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.592.4
Subject(s) - angiogenesis , neovascularization , microvessel , medicine , endocrinology , sprouting angiogenesis , diabetes mellitus , glycation , insulin , sprouting , insulin resistance , endothelial stem cell , biology , in vitro , biochemistry , botany
Understanding the effects of hyperglycemia on neovascular remodeling is critical especially considering the associated risk of heart disease, non‐healing wounds, and vascular dysfunction. Hyperglycemia has significant, and often contradictory, effects on endothelial cell activities related to neovascularization like endothelial cell proliferation, migration and tube formation. Therefore, it is unclear if the impairment of neovascularization due to hyperglycemia in vivo, involves altered angiogenic sprouting or possibly later post‐angiogenesis maturation and remodeling events. We examined early angiogenic events in a microvascular construct‐based in vitro angiogenesis model over a range of glucose concentrations. Acute hyperglycemia over 5 days did not alter the initial sprout formation. Interestingly, the absence of insulin caused a reduction in microvessel survival and sprouting. This reduction could be partially reversed by addition of IGF but not by DMAQB1, a metabolic insulin analogue. This study demonstrates the resistance of initial microvascular sprouting to acute hyperglycemia and highlights the growth factor like role for insulin in addition to its metabolic effects in neovessel formation. The role of chronic hyperglycemia and matrix glycation must also be examined to fully understand the role of diabetes on microvascular remodeling. Funded by NIH R01 DK078175 , R01 EB077683.