Bone-Derived Factors: A New Gateway to Regulate Glycemia.
Type 2 diabetes mellitus (T2DM) and osteoporosis are two major disorders which prevalence increases with aging and is predicted to worsen in the coming years. Preclinical investigations suggest common mechanisms implicated in the pathogenesis of both disorders. Recent evidence has established that there is a clear link between glucose and bone metabolism. The emergence of bone as an endocrine regulator through FGF23 and osteocalcin has led to the re-evaluation of the role of bone cells and bone-derived factors in the development of metabolic diseases such as T2DM. The development of bone morphogenetic proteins, fibroblast growth factor 23, and osteoprotegerin-deficient mice has allowed to elucidate their role in bone homeostasis, as well as revealed their potential important function in glucose homeostasis. This review proposes emerging perspectives for several bone-derived factors that may regulate glycemia through the activation or inhibition of bone remodeling or directly by regulating function of key organs such as pancreatic beta cell proliferation, insulin expression and secretion, storage and release of glucose from the liver, skeletal muscle contraction, and browning of the adipose tissue. Connections between organs including bone-derived factors should further be explored to understand the pathophysiology of glucose metabolism and diabetes.
Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, 64 Av de la Roseraie, 1205, Geneva 14, Switzerland. Nicolas.Bonnet@unige.ch.
Nicolas
N
Bonnet
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D006801:Humans; D051379:Mice; D010024:Osteoporosis / Q000150:complications / Q000378:metabolism*
D001786:Blood Glucose; C000717427:FGF23 protein, human; C000717428:Fgf23 protein, mouse; D000089703:Fibroblast Growth Factor-23
Beta-cell; Browning; Glucose; Insulin; Osteokine; Steatosis