Activation of alpha1A-adrenoceptor by andrographolide to increase glucose uptake in cultured myoblast C2C12 cells.
We investigated the mechanism of the plasma glucose lowering action of andrographolide, using radioactive glucose uptake into cultured myoblast C2C12 cells as the indicator. In C2C12 cells, andrographolide increased the radioactive glucose uptake in a concentration-dependent manner that was abolished by pretreatment with prazosin. Activation of alpha1-adrenoceptors by andrographolide was further indicated by the displacement of the [3H]prazosin binding in C2C12 cells. The alpha1A-adrenoceptor appears to have caused the displacement, because RS17053 abolished this andrographolide-stimulated glucose uptake at concentrations sufficient to block the alpha1A-adrenoceptor. Inhibition of phospholipase C (PLC) with U73312 concentration-dependently decreased under the action of andrographolide in C2C12 cells. This inhibition of glucose uptake by U73122 was specific because the inactive congener, U73343, failed to influence the action of andrographolide. Moreover, both chelerythrine and GF 109203X diminished the action of andrographolide at concentrations sufficient to inhibit protein kinase C (PKC). Our data suggest that an activation of alpha1A-AR by andrographolide in C2C12 cells may increase the glucose uptake via the PLC-PKC pathway.
Hsu
Jen-Hao
JH
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung City, Taiwan.
Liou
Shorong-Shii
SS
Yu
Bu-Chin
BC
Cheng
Juei-Tang
JT
Wu
Yang-Chang
YC
D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D035685:Andrographis; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D008517:Phytotherapy; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D004224:Diterpenes; D004791:Enzyme Inhibitors; D011942:Receptors, Adrenergic, alpha; C030419:andrographolide; D010738:Type C Phospholipases; D005947:Glucose