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c1q/TNF-related Protein-12 (CTRP12), A Novel Adipokine that Improves Insulin Sensitivity and Glycemic Control in Mouse Models of Obesity and Diabetes
The Journal of Biological Chemistry (2012)
  • Jonathan M. Peterson, Johns Hopkins University School of Medicine
  • Zhikui Wei, Johns Hopkins University School of Medicine
  • Xia Lei, Johns Hopkins University School of Medicine
  • Liudmila Cebotaru, Johns Hopkins University School of Medicine
  • Michael J. Wolfgang, Johns Hopkins University School of Medicine
  • G. Christian Baldeviano, Johns Hopkins University School of Medicine
  • G. William Wong, Johns Hopkins University School of Medicine
Abstract
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.

Keywords
  • adipokines,
  • adipose tissue,
  • akt,
  • diabetes,
  • insulin resistance,
  • obesity
Publication Date
March 23, 2012
DOI
10.1074/jbc.M111.303651
Publisher Statement
© 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Author’s may post the final edited PDFs created by the publisher to their own Web sites 12 months after publication. This document was originally published in Journal of Biological Chemistry.
Citation Information
Jonathan M. Peterson, Zhikui Wei, Xia Lei, Liudmila Cebotaru, et al.. "c1q/TNF-related Protein-12 (CTRP12), A Novel Adipokine that Improves Insulin Sensitivity and Glycemic Control in Mouse Models of Obesity and Diabetes" The Journal of Biological Chemistry Vol. 287 Iss. 13 (2012) p. 10301 - 10315 ISSN: 1083-351X
Available at: http://works.bepress.com/jonathan-peterson/6/