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Wei, Z, Peterson, JM, Lei, X, Cebotaru, L, Wolfgang, MJ, Baldeviano, GC and Wong, GW (2012) C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J. Biol. Chem. 287:10301-15


Despite the prevalence of insulin resistance and type 2 diabetes mellitus, their underlying mechanisms remain incompletely understood. Many secreted endocrine factors and the intertissue cross-talk they mediate are known to be dysregulated in type 2 diabetes mellitus. Here, we describe CTRP12, a novel adipokine with anti-diabetic actions. The mRNA and circulating levels of CTRP12 were decreased in a mouse model of obesity, but its expression in adipocytes was increased by the anti-diabetic drug rosiglitazone. A modest rise in circulating levels of CTRP12 by recombinant protein administration was sufficient to lower blood glucose in wild-type, leptin-deficient ob/ob, and diet-induced obese mice. A short term elevation of serum CTRP12 by adenovirus-mediated expression improved glucose tolerance and insulin sensitivity, normalized hyperglycemia and hyperinsulinemia, and lowered postprandial insulin resistance in obese and diabetic mice. CTRP12 improves insulin sensitivity in part by enhancing insulin signaling in the liver and adipose tissue. Further, CTRP12 also acts in an insulin-independent manner; in cultured hepatocytes and adipocytes, CTRP12 directly activated the PI3K-Akt signaling pathway to suppress gluconeogenesis and promote glucose uptake, respectively. Collectively, these data establish CTRP12 as a novel metabolic regulator linking adipose tissue to whole body glucose homeostasis through insulin-dependent and independent mechanisms.


PubMed PMC3322967 Online version:10.1074/jbc.M111.303651


Adenoviridae; Adipocytes/metabolism; Adipocytes/pathology; Adipokines/blood; Adipokines/genetics; Adipose Tissue/metabolism; Adipose Tissue/pathology; Animals; Cells, Cultured; Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/genetics; Diabetes Mellitus, Experimental/pathology; Disease Models, Animal; Gluconeogenesis/genetics; Hepatocytes/metabolism; Hepatocytes/pathology; Homeostasis/genetics; Humans; Insulin/genetics; Insulin/metabolism; Male; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred DBA; Mice, Obese; Obesity/blood; Obesity/genetics; Obesity/pathology; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Proto-Oncogene Proteins c-akt/genetics; Proto-Oncogene Proteins c-akt/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Signal Transduction/genetics; Transduction, Genetic