Involvement of regucalcin in lipid metabolism and diabetes

• Published in: Metabolism, clinical and experimental clinical and experimental, 2013-08, Vol.62 (8), p.1045-1051
• Main Authors: Yamaguchi, Masayoshi, Murata, Tomiyasu
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Calcium-Binding Proteins - physiology; Diabetes; Diabetes Mellitus - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinology & Metabolism; Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Fatty Liver - metabolism; Feeding. Feeding behavior; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - physiology; Humans; Insulin - physiology; Insulin resistance; Insulin Resistance - physiology; Intracellular Signaling Peptides and Proteins - physiology; Lipid metabolic disorder; Lipid Metabolism - physiology; Lipid Metabolism Disorders - metabolism; Liver - metabolism; Medical sciences; Regucalcin; RGN; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0026-0495; 1532-8600
• DOI: 10.1016/j.metabol.2013.01.023

Abstract Regucalcin (RGN/SMP30) was originally discovered in 1978 as a unique calcium-binding protein that does not contain the EF-hand motif of calcium-binding domain. The regucalcin gene ( rgn ) is localized on the X chromosome and is identified in over 15 species consisting the regucalcin family. Regucalcin has been shown to play a multifunctional role in cell regulation; maintaining of intracellular calcium homeostasis and suppressing of signal transduction, translational protein synthesis, nuclear deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) synthesis, proliferation, and apoptosis in many cell types. Moreover, regucalcin may play a pathophysiological role in metabolic disorder. The expression of regucalcin is stimulated through the action of insulin in liver cells in vitro and in vivo and it is decreased in the liver of rats with type I diabetes induced by streptozotocin administration in vivo. Overexpression of endogenous regucalcin stimulates glucose utilization and lipid production in liver cells with glucose supplementation in vitro. Regucalcin reveals insulin resistance in liver cells. Deficiency of regucalcin induces an impairment of glucose tolerance and lipid accumulation in the liver of mice in vivo. Overexpression of endogenous regucalcin has been shown to decrease triglyceride, total cholesterol and glycogen contents in the liver of rats, inducing hyperlipidemia. Leptin and adiponectin mRNA expressions in the liver tissues are decreased in regucalcin transgenic rats. Decrease in hepatic regucalcin is associated with the development and progression of nonalcoholic fatty liver disease and fibrosis in human patients. Regucalcin may be a key molecule in lipid metabolic disorder and diabetes.