Endogenous glucose production is inhibited by the adipose-derived protein Acrp30

Terry P. Combs, Anders H. Berg, Silvana Obici, Philipp E. Scherer, Luciano Rossetti

Research output: Contribution to journalArticle

716 Citations (Scopus)

Abstract

Intraperitoneal injection of purified recombinant Acrp30 lowers glucose levels in mice. To gain insight into the mechanism(s) of this hypoglycemic effect, purified recombinant Acrp30 was infused in conscious mice during a pancreatic euglycemic clamp. In the presence of physiological hyperinsulinemia, this treatment increased circulating Acrp30 levels by approximately twofold and stimulated glucose metabolism. The effect of Acrp30 on in vivo insulin action was completely accounted for by a 65% reduction in the rate of glucose production. Similarly, glucose flux through glucose-6 phosphatase (G6Pase) decreased with Acrp30, whereas the activity of the direct pathway of glucose 6-phosphate biosynthesis, an index of hepatic glucose phosphorylation, increased significantly. Acrp30 did not affect the rates of glucose uptake, glycolysis, or glycogen synthesis. These results indicate that an acute increase in circulating Acrp30 levels lowers hepatic glucose production without affecting peripheral glucose uptake. Hepatic expression of the gluconeogenic enzymes phospho enolpyruvate carboxykinase and G6Pase mRNAs was reduced by more than 50% following Acrp30 infusion compared with vehicle infusion. Thus, a moderate rise in circulating levels of the adipose derived protein Acrp30 inhibits both the expression of hepatic gluconeogenic enzymes and the rate of endogenous glucose production.

Original languageEnglish (US)
Pages (from-to)1875-1881
Number of pages7
JournalJournal of Clinical Investigation
Volume108
Issue number12
DOIs
StatePublished - 2001

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Glucose
Proteins
Glucose-6-Phosphatase
Liver
Glucose-6-Phosphate
Glucose Clamp Technique
Hyperinsulinism
Glycolysis
Enzymes
Intraperitoneal Injections
Glycogen
Hypoglycemic Agents
Phosphorylation
Insulin
Messenger RNA

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. / Combs, Terry P.; Berg, Anders H.; Obici, Silvana; Scherer, Philipp E.; Rossetti, Luciano.

In: Journal of Clinical Investigation, Vol. 108, No. 12, 2001, p. 1875-1881.

Research output: Contribution to journalArticle

Combs, Terry P. ; Berg, Anders H. ; Obici, Silvana ; Scherer, Philipp E. ; Rossetti, Luciano. / Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. In: Journal of Clinical Investigation. 2001 ; Vol. 108, No. 12. pp. 1875-1881.
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