GONUTS has been updated to MW1.31 Most things seem to be working but be sure to report problems.

Have any questions? Please email us at ecoliwiki@gmail.com

PMID:22275362

From GONUTS
Jump to: navigation, search
Citation

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

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.

Links

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

Keywords

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

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:ADIPL

enables

GO:0005179: hormone activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:ADIPL

located_in

GO:0005576: extracellular region

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:ADIPL

involved_in

GO:0046324: regulation of glucose import

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADIPL

located_in

GO:0005615: extracellular space

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:35770)

Seeded From UniProt

complete

MOUSE:ADIPL

acts_upstream_of_or_within

GO:0051897: positive regulation of protein kinase B signaling

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:ADIPL

acts_upstream_of_or_within

GO:0046628: positive regulation of insulin receptor signaling pathway

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:ADIPL

acts_upstream_of_or_within

GO:0046326: positive regulation of glucose import

ECO:0000315: mutant phenotype evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000136)

Seeded From UniProt

complete

MOUSE:ADIPL

acts_upstream_of_or_within

GO:0045721: negative regulation of gluconeogenesis

ECO:0000314: direct assay evidence used in manual assertion

P

  • regulates_o_occurs_in:(CL:0000182)

Seeded From UniProt

complete

MOUSE:ADIPL

acts_upstream_of_or_within

GO:0035774: positive regulation of insulin secretion involved in cellular response to glucose stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

See Help:References for how to manage references in GONUTS.