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- Title
Caveolin improves glucose metabolism in diabetic mice.
- Authors
Otsu, Koji; Toya, Yoshiyuki; Oshikawa, Jin; Sakata, Masahiro; Yazawa, Takuya; Okumura, Satoshi; Sato, Motohiko; Umemura, Satoshi; Minamisawa, Susumu; Ishikawa, Yoshihiro
- Abstract
The caveolin family of the membrane anchoring proteins accumulates various growth receptors in caveolae and inhibits their function. Here, we identify caveolin as a potent enhancer of insulin signal when overexpressed in the liver in vivo, where endogenous caveolin is little expressed. Adenovirus-mediated caveolin-3 gene transfer to the liver led to a marked increase in hepatic glycogen synthesis in diabetic mice (to 468.5 +219.3%, p<0.05, n=4), but not in non-diabetic lean mice, and was accompanied by a decrease in mRNA expression of PEPCK (to 49.2 +10.9%, p<0.05, n=5) and an increase in that of Gck (to 166.9 +21.1%, p<0.05, n=5). There was a marked increase in insulin sensitivity in diabetic obese mice as exemplified by decreased fasting blood glucose levels (to 82.1 +2.6%, p<0.05, n=8) and improved glucose tolerant test performance. These effects were attributed mostly to increased insulin receptor activity and caveolin-mediated, direct inhibition of PTP1B activity (to 52.9 +2.2%, p<0.05, n=4), of which expression was significantly increased in obese mouse liver (to 195.0 +28.1%, p<0.05, n=4). Overexpression of caveolin-3 in hepatic cells enhanced the insulin receptor signal as well. Our results suggest that caveolin-3 is an important, endogenous regulator of glucose metabolism that can enhance insulin signal, in particular, under pathological conditions where phosphatase activity is upregulated.
- Subjects
MEMBRANE proteins; INSULIN; DIABETES; BLOOD sugar; GLUCOSE; METABOLISM; MOUSE diseases
- Publication
FASEB Journal, 2007, Vol 21, Issue 6, pA833
- ISSN
0892-6638
- Publication type
Article