TY - JOUR
T1 - Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action
AU - Rossetti, Luciano
AU - Massillon, Duna
AU - Barzilai, Nir
AU - Vuguin, Patricia
AU - Chen, Wei
AU - Hawkins, Meredith
AU - Wu, Jie
AU - Wang, Jali
PY - 1997/10/31
Y1 - 1997/10/31
N2 - Long term administration of leptin decreases caloric intake and fat mass and improves glucose tolerance. Here we examine whether leptin acutely regulates peripheral and hepatic insulin action. Recombinant mouse leptin (0.3 mg/kg · h, Leptin +) or vehicle (Leptin -) were administered for 6 h to 4-month-old rats (n = 20), and insulin (3 milliunits/kg · min) clamp studies were performed. During physiologic hyperinsulinemia (plasma insulin ~65 microunits/ml), the rates of whole body glucose uptake, glycolysis, and glycogen syntheses and the rates of 2-deoxyglucose uptake in individual tissues were similar in Leptin - and Leptin +. Post-absorptive hepatic glucose production (HGP) was similar in the two groups. However, leptin enhanced insulin's inhibition of HGP (4.1 ± 0.7 and 6.2 ± 0.7 mg/kg · min; p < 0.05). The decreased HGP in the Leptin + group was due to a marked suppression of hepatic glycogenolysis (0.7 ± 0.1 versus 4.1 ± 0.6 mg/kg · min, in Leptin + versus Leptin -, respectively; p < 0.001), whereas the % contribution of gluconeogenesis to HGP was markedly increased (82 ± 3% versus 36 ± 4% in Leptin + and Leptin -, respectively; p < 0.001). At the end of the 6-h leptin infusion, the hepatic abundance of glucokinase mRNA was decreased, whereas that of phosphoenolpyruvate carboxykinase mRNA was increased compared with Leptin -. We conclude that an acute increase in plasma leptin 1) enhances insulin's ability to inhibit HGP, 2) does not affect peripheral insulin action, and 3) induces a redistribution of intrahepatic glucose fluxes and changes in the gene expression of hepatic enzymes that closely resemble those of fasting.
AB - Long term administration of leptin decreases caloric intake and fat mass and improves glucose tolerance. Here we examine whether leptin acutely regulates peripheral and hepatic insulin action. Recombinant mouse leptin (0.3 mg/kg · h, Leptin +) or vehicle (Leptin -) were administered for 6 h to 4-month-old rats (n = 20), and insulin (3 milliunits/kg · min) clamp studies were performed. During physiologic hyperinsulinemia (plasma insulin ~65 microunits/ml), the rates of whole body glucose uptake, glycolysis, and glycogen syntheses and the rates of 2-deoxyglucose uptake in individual tissues were similar in Leptin - and Leptin +. Post-absorptive hepatic glucose production (HGP) was similar in the two groups. However, leptin enhanced insulin's inhibition of HGP (4.1 ± 0.7 and 6.2 ± 0.7 mg/kg · min; p < 0.05). The decreased HGP in the Leptin + group was due to a marked suppression of hepatic glycogenolysis (0.7 ± 0.1 versus 4.1 ± 0.6 mg/kg · min, in Leptin + versus Leptin -, respectively; p < 0.001), whereas the % contribution of gluconeogenesis to HGP was markedly increased (82 ± 3% versus 36 ± 4% in Leptin + and Leptin -, respectively; p < 0.001). At the end of the 6-h leptin infusion, the hepatic abundance of glucokinase mRNA was decreased, whereas that of phosphoenolpyruvate carboxykinase mRNA was increased compared with Leptin -. We conclude that an acute increase in plasma leptin 1) enhances insulin's ability to inhibit HGP, 2) does not affect peripheral insulin action, and 3) induces a redistribution of intrahepatic glucose fluxes and changes in the gene expression of hepatic enzymes that closely resemble those of fasting.
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U2 - 10.1074/jbc.272.44.27758
DO - 10.1074/jbc.272.44.27758
M3 - Article
C2 - 9346919
AN - SCOPUS:0030784253
SN - 0021-9258
VL - 272
SP - 27758
EP - 27763
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 44
ER -