Showing papers by "Clay F. Semenkovich published in 2000"

Skeletal muscle respiratory uncoupling prevents diet-induced obesity and insulin resistance in mice.

Abstract: To determine whether uncoupling respiration from oxidative phosphorylation in skeletal muscle is a suitable treatment for obesity and type 2 diabetes, we generated transgenic mice expressing the mitochondrial uncoupling protein (Ucp) in skeletal muscle. Skeletal muscle oxygen consumption was 98% higher in Ucp-L mice (with low expression) and 246% higher in Ucp-H mice (with high expression) than in wild-type mice. Ucp mice fed a chow diet had the same food intake as wild-type mice, but weighed less and had lower levels of glucose and triglycerides and better glucose tolerance than did control mice. Ucp-L mice were resistant to obesity induced by two different high-fat diets. Ucp-L mice fed a high-fat diet had less adiposity, lower levels of glucose, insulin and cholesterol, and an increased metabolic rate at rest and with exercise. They were also more responsive to insulin, and had enhanced glucose transport in skeletal muscle in the setting of increased muscle triglyceride content. These data suggest that manipulating respiratory uncoupling in muscle is a viable treatment for obesity and its metabolic sequelae.

Exercise induces lipoprotein lipase and GLUT-4 protein in muscle independent of adrenergic-receptor signaling

Abstract: Exercise increases the expression of lipoprotein lipase (LPL) and GLUT-4 in skeletal muscle. Intense exercise increases catecholamines, and catecholamines without exercise can affect the expression...

The role of osteoprogenitors in vascular calcification.

Abstract: Calcification is a component of vascular disease that usually occurs in concert with atheroma formation but through distinct pathophysiological processes. Vessel wall osteoprogenitor cells known as calcifying vascular cells can form bone matrix proteins and calcified nodules, analogous to osteoblastic differentiation in bone. These cells have been isolated from the tunica media of bovine and human arteries, and both in-vitro tissue culture models and mouse models of vascular calcification have been established. Studies of the effects of diabetes mellitus, hyperlipidemia, estrogens and glucocorticoids on calcifying vascular cell function provide insight into the relationship between common human disease states and vascular calcification.

Diabetes Mellitus and Vascular Disease Risk

Abstract: Diabetes mellitus is a complex, multifactorial disorder that has an overall prevalence of about 5% in the United States. Whereas approximately 90% of diabetics have type II, or non-insulin-dependent diabetes mellitus (NIDDM), the remainder have type I, or insulin-dependent diabetes mellitus (IDDM). The prevalence of diabetes varies greatly among different ethnic groups, with rates as high as 20% in some Asian-Indian and American-Indian populations. These wide variations in prevalence are accounted for mainly by NIDDM Although the cause or causes of NIDDM are not known, the environment is clearly very important. The molecular basis for IDDM is better defined, but the primary cause remains unclear. Despite the etiologic and pathogenic differences between NIDDM and IDDM, the chronic sequelae of both forms of diabetes are the same, and vascular disease, particularly coronary heart disease (CHD), is the major cause of morbidity and mortality in diabetic patients.