Impairment of organ perfusion in metabolic disease
The goal of our current research in the Laboratory for Physiology and the ICaR-VU is to elucidate the causes of impaired organ perfusion in obesity and type 2 diabetes, and to translate this knowledge into prevention of type 2 diabetes and associated vital organ failure.
To this end, we have developed a translational research line in close collaboration with several clinical departments, combining human physiology research (muscle perfusion, insulin sensitivity) with models of obesity, insulin resistance, type 2 diabetes, and kidney failure.
We have discovered that impaired muscle perfusion is strongly and causally related to insulin sensitivity, and that the characteristics of fat tissue control muscle perfusion through distinct signaling pathways in endothelium. Our recent research has shown that perivascular adipose tissue, situated around arteries and arterioles, is contributes to regulation of muscle perfusion, and that its vasodilator functions deteriorate during the development of obesity and type 2 diabetes.
Current research targets the roles of 5’AMP-activated protein kinase and inflammatory signaling in interactions of PVAT with cardiovascular and metabolic disease and the role of fibroblast growth factor 23 (FGF23) in cardiovascular complications of kidney failure
Selection of recent publications
Meijer,RI, Bakker,W, Alta,CL, Sipkema,P, Yudkin,JS, Viollet,B, Richter,EA, Smulders,YM, van Hinsbergh,VW, Serne,EH, Eringa,EC. Perivascular adipose tissue control of insulin-induced vasoreactivity in muscle is impaired in db/db mice. Diabetes 62:590-598, 2013
Aman,J, van,BJ, Damanafshan,A, Huveneers,S, Eringa,EC, Vogel,SM, Groeneveld,AB, Vonk,NA, van Hinsbergh,VW, van Nieuw Amerongen,GP. Effective treatment of edema and endothelial barrier dysfunction with imatinib. Circulation 126:2728-2738, 2012
Meijer,RI, de Boer,MP, Groen,MR, Eringa,EC, Rattigan,S, Barrett,EJ, Smulders,YM, Serne,EH. Insulin-induced microvascular recruitment in skin and muscle are related and both are associated with whole-body glucose uptake. Microcirculation 19:494-500, 2012
Bakker,W, Sipkema,P, Stehouwer,CD, Serne,EH, Smulders,YM, van Hinsbergh,VW, Eringa,EC. Protein kinase C theta activation induces insulin-mediated constriction of muscle resistance arteries. Diabetes 57:706-713, 2008
Yudkin,JS, Eringa,E, Stehouwer,CD. “Vasocrine” signalling from perivascular fat: a mechanism linking insulin resistance to vascular disease. Lancet 365:1817-1820, 2005