warfarin and Insulin-Resistance

Recent studies have indicated that osteocalcin, a peptide secreted by osteoblasts, functions as an anti-diabetogenic hormone in mice. Osteocalcin knock out mice exhibit obesity, hyperglycemia, and decreased insulin secretion relative to wild-type mice. Treatment with non-carboxylated osteocalcin upregulates energy expenditure, and ameliorates obesity and diabetes in mouse models of obesity-related diabetes. Of interest, the beneficial effects of osteocalcin were shown to be specific to non-carboxylated osteocalcin. This appears, however, inconsistent with recent clinical studies showing insulin-sensitizing effects of vitamin K, which promotes gamma-carboxylation of osteocalcin. These findings shed new light on the crosstalk between bone and energy expenditure, and lead to new questions. These questions include: (1) Does non-carboxylated osteocalcin exert the beneficial effects in humans?; (2) Does warfarin, a vitamin K antagonist, improve insulin, sensitivity and lower blood glucose levels?; (3) and Do estrogen and bisphosphonate, which reduce circulating osteocalcin, contribute to insulin resistance and obesity? These issues await further investigations.

Topics: Animals; Bone Density Conservation Agents; Diabetes Mellitus; Diphosphonates; Estrogens; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin Resistance; Mice; Obesity; Osteoblasts; Osteocalcin; Vitamin K; Warfarin

To investigate the possible protective effect of elevated undercarboxylated osteocalcin on diabetic cardiomyopathy mechanisms and risk factors.. In all, 32 male rats were divided into four groups: control, diabetic, diabetic warfarin and normal warfarin-treated groups. Isolated heart functions were assessed; fasting serum insulin, glucose and glycosylated haemoglobin, homeostasis model assessment insulin resistance and lipid profile were investigated. Serum undercarboxylated osteocalcin and adiponectin were also measured. In cardiac tissue, malondialdehyde content, acyl-CoA dehydrogenase gene expression, Bax/Bcl2 ratio, sarcoendoplasmic reticulum calcium ATPase and osteocalcin receptor (G protein-coupled receptor family C group 6 member A) genes expression were investigated.. Prophylactic elevation of undercarboxylated osteocalcin was accompanied by improved insulin sensitivity and lipid profile, increased serum adiponectin, upregulated myocardial osteocalcin receptor with preserved left ventricular function, decreased cardiac malondialdehyde content, acyl-CoA dehydrogenase and Bax/Bcl2 ratio.. Undercarboxylated osteocalcin was suggested to have protective effects against diabetic cardiomyopathy, possibly through direct action on upregulated G protein-coupled receptor family C group 6 member A and indirectly via adiponectin. These effects may be mediated through antagonizing oxidative stress and apoptosis.

Topics: Adiponectin; Animals; Apoptosis; Apoptosis Regulatory Proteins; Biomarkers; Blood Glucose; Carbon-Carbon Ligases; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Enzyme Inhibitors; Insulin; Insulin Resistance; Lipids; Male; Malondialdehyde; Myocardium; Osteocalcin; Oxidative Stress; Rats; Receptors, G-Protein-Coupled; Signal Transduction; Warfarin