Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle

FASEB J. 2006 Jul;20(9):1570-2. doi: 10.1096/fj.05-4780fje.

Abstract

Diabetes alters microvascular structure and function and is a major risk factor for cardiovascular diseases. In diabetic skeletal muscle, impaired angiogenesis and reduced VEGF-A expression have been observed, whereas in healthy muscle exercise is known to have opposite effects. We studied the effects of type 1 diabetes and combined exercise training on angiogenic mRNA expression and capillarization in mouse skeletal muscle. Microarray and real-time PCR analyses showed that diabetes altered the expression of several genes involved in angiogenesis. For example, levels of proangiogenic VEGF-A, VEGF-B, neuropilin-1, VEGFR-1, and VEGFR-2 were reduced and the levels of antiangiogenic thrombospondin-1 and retinoblastoma like-2 were increased. Exercise training alleviated some of these changes, but could not completely restore them. VEGF-A protein content was also reduced in diabetic muscles. In line with the reduced levels of VEGF-A and other angiogenic factors, and increased levels of angiogenesis inhibitors, capillary-to-muscle fiber ratio was lower in diabetic mice compared to healthy controls. Exercise training could not restore capillarization in diabetic mice. In conclusion, these data illustrate that type 1 diabetes is associated with reduced skeletal muscle capillarization and the dysregulation of complex angiogenesis pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inducing Agents
  • Animals
  • Capillaries / physiology*
  • Diabetes Mellitus, Experimental / physiopathology*
  • Diabetes Mellitus, Type 1 / physiopathology*
  • Disease Models, Animal
  • Gene Expression Regulation*
  • Male
  • Mice
  • Mice, Inbred Strains
  • Muscle, Skeletal / blood supply
  • Muscle, Skeletal / physiopathology*
  • Neovascularization, Pathologic / genetics*
  • Neovascularization, Pathologic / prevention & control
  • Neovascularization, Physiologic / genetics*
  • Physical Conditioning, Animal*
  • Ribonuclease, Pancreatic / physiology*

Substances

  • Angiogenesis Inducing Agents
  • angiogenin
  • Ribonuclease, Pancreatic