[Is ucOC a novel bone-derived anti-diabetogenic hormone in humans?].
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.
Kaneki
Masao
M
Department of Anesthesia & Critical Care, Massachusetts General Hospital, Harvard Medical School, MA, USA.
D000818:Animals; D050071:Bone Density Conservation Agents; D003920:Diabetes Mellitus / Q000188:drug therapy; D004164:Diphosphonates; D004967:Estrogens; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology; D007004:Hypoglycemic Agents; D007333:Insulin Resistance; D051379:Mice; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism / Q000502:physiology* / Q000627:therapeutic use; D014812:Vitamin K / Q000502:physiology; D014859:Warfarin
D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D004967:Estrogens; D007004:Hypoglycemic Agents; D015675:Osteocalcin; D014812:Vitamin K; D014859:Warfarin