Abstract
STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.
| Original language | English |
|---|---|
| Pages (from-to) | 267-275 |
| Number of pages | 9 |
| Journal | Cell Metabolism |
| Volume | 3 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 2006 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Physiology
Cite this
Role of hepatic STAT3 in brain-insulin action on hepatic glucose production. / Inoue, Hiroshi; Ogawa, Wataru; Asakawa, Akihiro; Okamoto, Yasuo; Nishizawa, Akihiko; Matsumoto, Michihiro; Teshigawara, Kiyoshi; Matsuki, Yasushi; Watanabe, Eijiro; Hiramatsu, Ryuji; Notohara, Kenji; Katayose, Koji; Okamura, Hitoshi; Kahn, C. Ronald; Noda, Tetsuo; Takeda, Kiyoshi; Akira, Shizuo; Inui, Akio; Kasuga, Masato.
In: Cell Metabolism, Vol. 3, No. 4, 04.2006, p. 267-275.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of hepatic STAT3 in brain-insulin action on hepatic glucose production
AU - Inoue, Hiroshi
AU - Ogawa, Wataru
AU - Asakawa, Akihiro
AU - Okamoto, Yasuo
AU - Nishizawa, Akihiko
AU - Matsumoto, Michihiro
AU - Teshigawara, Kiyoshi
AU - Matsuki, Yasushi
AU - Watanabe, Eijiro
AU - Hiramatsu, Ryuji
AU - Notohara, Kenji
AU - Katayose, Koji
AU - Okamura, Hitoshi
AU - Kahn, C. Ronald
AU - Noda, Tetsuo
AU - Takeda, Kiyoshi
AU - Akira, Shizuo
AU - Inui, Akio
AU - Kasuga, Masato
PY - 2006/4
Y1 - 2006/4
N2 - STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.
AB - STAT3 regulates glucose homeostasis by suppressing the expression of gluconeogenic genes in the liver. The mechanism by which hepatic STAT3 is regulated by nutritional or hormonal status has remained unknown, however. Here, we show that an increase in the plasma insulin concentration, achieved either by glucose administration or by intravenous insulin infusion, stimulates tyrosine phosphorylation of STAT3 in the liver. This effect of insulin was mediated by the hormone's effects in the brain, and the increase in hepatic IL-6 induced by the brain-insulin action is essential for the activation of STAT3. The inhibition of hepatic glucose production and of expression of gluconeogenic genes induced by intracerebral ventricular insulin infusion was impaired in mice with liver-specific STAT3 deficiency or in mice with IL-6 deficiency. These results thus indicate that IL-6-STAT3 signaling in the liver contributes to insulin action in the brain, leading to the suppression of hepatic glucose production.
UR - http://www.scopus.com/inward/record.url?scp=33645579324&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645579324&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2006.02.009
DO - 10.1016/j.cmet.2006.02.009
M3 - Article
C2 - 16581004
AN - SCOPUS:33645579324
VL - 3
SP - 267
EP - 275
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 4
ER -