Regulators for blood glucose level affect gene expression of aquaporin 3.
Aquaporin 3 (AQP3), a membrane protein, is known to permeabilize water and other small molecules such as glycerol and urea and is localized in the bowel, skin, kidney, and erythrocytes. Since glycerol is a nutrient and serves as a source material in glycolytic metabolism, absorption of glycerol in the gastrointestinal tract may be under some control. Therefore we first investigated whether insulin regulating the glycolytic pathway took part in glycerol transport through AQP3 in the gastrointestinal tract and found that insulin significantly suppressed mRNA and protein expressions of AQP3 in Caco-2 cells. The antidiabetic drugs troglitazone and tolbutamide were also observed to suppress significantly AQP3 expression, but the biguanides metformin and buformin did not induce such suppression. Epinephrine was found to increase expression of AQP3, although glucagon showed no change of expression. Wortmannin and rapamycin were demonstrated to deactivate suppression of AQP3 expression by insulin and troglitazone, suggesting that the signal transducers, phosphoinositide 3 kinase (PI3K) and the mammalian target of rapamycin (mTOR), are involved in the signal pathway for regulating transcription of AQP3.
Asai
Mariko
M
Department of Pharmaceutics, Gifu Pharmaceutical University, Japan.
Higuchi
Shouta
S
Kubota
Masafumi
M
Iguchi
Kazuhiro
K
Usui
Shigeyuki
S
Hirano
Kazuyuki
K
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D051400:Aquaporin 3 / Q000096:biosynthesis* / Q000235:genetics*; D001645:Biguanides / Q000494:pharmacology; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D018938:Caco-2 Cells; D002839:Chromans / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007329:Insulin Antagonists / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D045162:Thiazolidinediones / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D000077288:Troglitazone; D000077191:Wortmannin
D000199:Actins; D000730:Androstadienes; D001645:Biguanides; D001786:Blood Glucose; D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D007329:Insulin Antagonists; D012333:RNA, Messenger; D045162:Thiazolidinediones; D051400:Aquaporin 3; D005934:Glucagon; D014044:Tolbutamide; D000077288:Troglitazone; D000077191:Wortmannin; D004837:Epinephrine