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

TP Combs, AH Berg, S Obici… - The Journal of …, 2001 - Am Soc Clin Investig
TP Combs, AH Berg, S Obici, PE Scherer, L Rossetti
The Journal of clinical investigation, 2001Am Soc Clin Investig
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 …
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 phosphoenolpyruvate 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.
The Journal of Clinical Investigation