Stimulatory effect of caffeic acid on α 1A -adrenoceptors to increase glucose uptake into cultured C 2 C 12 cells

Abstract

In an attempt to understand the antihyperglycemic action of caffeic acid, the myoblast C2C12 cells were employed to investigate the glucose uptake in the present study. Caffeic acid enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner. Similar effect of phenylephrine on the uptake of radioactive glucose was also observed in C2C12 cells. Prazosin attenuated the action of caffeic acid in a way parallel to the blockade of phenylephrine. Effect of caffeic acid on alpha1-adrenoceptors was further supported by the displacement of [3H]prazosin binding in C2C12 cells. Moreover, the glucose uptake-increasing action of phenylephrine in C2C12 cells was inhibited by the antagonists of alpha1A-adrenoceptors, both tamsulosin and WB 4101, but not by the antagonist of alpha1B-adrenoceptors, chlorethylclonidine (CEC). The presence of alpha1A-adrenoceptors in C2C12 cells can thus be considered. Similar inhibition of the action of caffeic acid was also obtained in C2C12 cells co-incubating these antagonists. An activation of alpha1A-adrenoceptors seems responsible for the action of caffeic acid in C2C12 cells. In the presence of U73312, the specific inhibitor of phospholipase C, caffeic acid-stimulated uptake of radioactive glucose into C2C12 cells was reduced in a concentration-dependent manner and it was not affected by U73343, the negative control of U73312. Moreover, chelerythrine and GF 109203X diminished the action of caffeic acid at concentrations sufficient to inhibit protein kinase C. Therefore, the obtained data suggest that an activation of alpha1A-adrenoceptors in C2C12 cells by caffeic acid may increase the glucose uptake via phospholipase C-protein kinase C pathway.

Effects of Orthosiphon stamineus aqueous extract on plasma glucose concentration and lipid profile in normal and streptozotocin-induced diabetic rats

“…Several phenolic compounds and flavonoid possess marked anti-diabetic activity (Hsu et al, 2000). In addition, caffeic acid, a phenolic compound, has been reported to increase glucose uptake in rat myocytes (Cheng and Liu, 2000). Our present results showed that Orthosiphon stamineus extract significantly reduced plasma glucose concentration in both normal and diabetic rats.…”

Drying alters the phenolic constituents, antioxidant properties, α‐amylase, and α‐glucosidase inhibitory properties of Moringa (Moringa oleifera) leaf

“…It has antifungal, antiviral, anticarcinogenic, anti‐inflammatory, antioxidant and antidiabetic properties (Shahrzad, Hodgson, & Narumi, 2001). Caffeic acid has also been reported to increase glucose uptake in rat myocytes (Cheng & Liu, 2000). Quercetin is one of the most common flavonoids occurring mainly in glycosidic forms such as rutin (Havsteen, 1983).…”

AMP-Activated Protein Kinase Activation by Adrenoceptors in L6 Skeletal Muscle Cells

“…Activation of AMPK is also not secondary to changes in PKC activity despite PKC being implicated in ␣ 1 -adrenoceptor mediation of glucose uptake (12,29). The phorbol ester TPA (which activates conventional and novel PKC isoforms) did not phosphorylate AMPK, and downregulation of conventional and novel PKCs with long-term TPA (33) or the use of PKC inhibitors did not affect the ability of cirazoline (or AICAR) to phosphorylate AMPK, suggesting that PKCs are not involved in phosphorylation of AMPK (PKC inhibition was also ineffective in inhibiting AICAR activation of AMPK in rat papillary muscle [45]).…”

“…These effects are blocked by guanethidine but not by adrenal medullation, showing that norepinephrine and not epinephrine mediates this response (24). Other studies performed in vivo and in vitro show that ␣-and ␤-adrenoceptor (12,15,(25)(26)(27)(28)(29) activation increases glucose uptake in skeletal muscle via an insulin-independent pathway. Hence it is likely that circulating epinephrine has vastly different actions on glucose uptake as opposed to focally released norepinephrine at the synaptic clefts, which can reach high concentrations.…”