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(The FASEB Journal. 2006;20:1570-1572.)
© 2006 FASEB

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

Riikka Kivelä*,{dagger},1, Mika Silvennoinen*,{dagger}, Anna-Maria Touvra{dagger}, T. Maarit Lehti*, Heikki Kainulainen*,{dagger} and Veikko Vihko*

* LIKES Research Center for Sport and Health Sciences, Jyväskylä, Finland; and

{dagger} Neuromuscular Research Center, Department of Biology of Physical Activity, University of Jyväskylä, Jyväskylä, Finland

1Correspondence: LIKES Research Center, Rautpohjankatu 8a, Jyväskylä FIN-40740, Finland. E-mail: riikka.kivela{at}likes.fi

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.—Kivelä, R., Silvennoinen, M., Touvra, A.-M., Lehti, T. M., Kainulainen, H., Vihko, V. Effects of experimental type 1 diabetes and exercise training on angiogenic gene expression and capillarization in skeletal muscle.




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