Biomedical subjects

Juei-Tang Cheng

Publications and source records attributed to Juei-Tang Cheng.

At least 37 records · Page 2Linked to original sources

PubMed2005

Mediation of beta-endorphin by myricetin to lower plasma glucose in streptozotocin-induced diabetic rats.

Streptozotocin-induced diabetic (STZ-diabetic) rats were employed to investigate the mechanism(s) whereby myricetin, the active principle of Abelmoschus moschatus (Malvaceae), exerts its glucose-lowering effects. Myricetin was purified from the aerial portion of the plant and administered intravenously. A dose-dependent decrease in plasma glucose concentration was observed 30 min following injection, in parallel with increased plasma beta-endorphin-like immunoreactivity (BER). Myricetin enhanced BER release similarly from isolated adrenal medulla. Plasma glucose-lowering and BER-elevating effects of myricetin were both eliminated after bilateral adrenalectomy. Myricetin failed to lower plasma glucose after treatment with opioid mu-receptor antagonists and in opioid mu-receptor knockout diabetic mice. Injection of myricetin three times daily for three consecutive days resulted in increased expression of the glucose transporter subtype 4 (GLUT 4) in soleus muscle and in reduced expression of phosphoenolpyruvate carboxykinase (PEPCK) in liver; these inductions were preventable by opioid mu-receptor blockade. Findings support the conclusion that the plasma glucose-lowering action of myricetin in insulin-deficient animals is mediated by activation of opioid mu-receptors of peripheral tissues in response to increased beta-endorphin secretion. Opioid mu-receptor activation is held responsible for the enhancement of muscle GLUT 4 gene expression and the attenuation of hepatic PEPCK gene expression observed in these myricetin-treated diabetic animals.

Abelmoschus↗

PubMed2005

Comparison of the antinociceptive action of crude Fuzei, the root of Aconitum, and its processed products.

The antinociceptive effects of crude Fuzei, the root of Aconitum carmichaeli and of Fuzei processed by three different methods were determined in mice and rats using the light tail-flick assay. A dose-dependent and significant increase in pain threshold was found at 60 min post treatment, with doses of 20-60 mg/kg crude Fuzei. The analgesic effects of processed Fuzei (20-60 mg/kg) exhibited a dose-dependent inhibition of tail-flick, but the effects were lower than those produced by crude Fuzei in the same tests. The analgesic effect of Yan-Fuzei, the salt baking product, was the most potent of the processed products and was nearly that provided by crude Fuzei. Although the concentrations of aconitine were significantly lower in the processed Fuzei than in the crude Fuzei, a higher oral LD50 was found for all of the processed Fuzei formulations. Moreover, antinociception of crude Fuzei and its processed products was attenuated but not totally blocked by naloxone at doses sufficient to block opioid mu-receptors. Furthermore, the analgesic effect of crude Fuzei and its processed products was decreased in opioid mu-receptor knockout mice, but the effect remained unaltered in mice with opioid mu-receptors, indicating that the analgesic effect of Fuzei is centrally mediated. These results demonstrate that Fuzei processed by salt baking possesses analgesic effects within a large therapeutic range, probably via a mechanism involving central opioid receptors that mediate the antinociception.

Aconitum↗

PubMed2005

The role of sorbitol pathway and treatment effect of aldose reductase inhibitor ONO2235 in the up-regulation of cardiac M2-muscarinic receptors in streptozotocin-induced diabetic rats.

This study investigated the role of the sorbitol pathway on the genetic up-regulation of the cardiac M(2) muscarinic receptor (M(2)-mAChR) in streptozotocin (STZ)-induced diabetic rats. Three-month-old male Wistar rats were divided into five groups: (1) normal controls; (2) rats rendered diabetic by streptozotocin; (3) rats fed with glucose; (4) rats injected with sorbitol; and (5) diabetic rats treated with ONO-2235, an aldose reductase inhibitor. The M(2) muscarinic receptor (M(2)-mAChR) protein and mRNA densities of the heart tissue were measured by Western immunoblotting and Northern blotting, respectively. The densities of M(2)-mAChR protein and mRNA in the heart were significantly increased in diabetic rats, and rats given either glucose or sorbitol. When diabetic rats were treated with ONO-2235, the increases in heart M(2)-mAChR protein and mRNA were significantly reduced. The findings suggest that hyperglycemia and the sorbitol pathway are involved in the pathogenesis of diabetic heart disease in STZ-induced diabetic rats. Aldose reductase inhibitors may be useful in the treatment and prevention of cardiac complication in diabetes.

Aldehyde Reductase↗

PubMed2005

Involvement of serotonin in the hypoglycemic response to 2 Hz electroacupuncture of zusanli acupoint (ST36) in rats.

In our previous studies, an insulin-dependent hypoglycemic effect produced by electroacupuncture (EA) was shown to be mediated by endogenous opioid peptides (EOP). In the present study, we applied 2 Hz EA to both zusanli acupoints (ST36) in the test group for 30 min, and to a nonacupoint area in the control group for 30 min to compare the acupoint specific character in the hypoglycemic effect of EA. Assays of plasma beta-endorphin and insulin levels were performed by ELISA kits. The insulin-dependent mechanism of the hypoglycemic effect was also investigated in streptozotocin (STZ)-induced diabetic rats. The mediation of EOP and the role of mu-opioid receptor were examined by naloxone and mu-opioid receptor knockout mice (MOR-KOM). The serotonin depletion was carried out by injecting (i.p.) p-chlorophenylalanine (PCPA); two low doses of serotonin were also injected (i.v.) to analyze the direct effect on plasma glucose levels. The hypoglycemic effect of EA was much greater in rats stimulated at ST36 than in rats receiving the same stimulation at the nonacupoint area. The plasma levels of insulin and beta-endorphin were also significantly elevated after stimulation of both zusanli acupoints, but remained unchanged following stimulation at the nonacupoint area. There was no sharp hypoglycemic response to 2 Hz EA at zusanli acupoint of STZ-induced diabetic rats. However, the hypoglycemic effect of this EA was not totally blocked by the sufficient dose of naloxone (1 mg/kg, i.v.). Additionally, 2 Hz EA at ST36 also showed a sharp decrease in plasma glucose levels of MOR-KOM. Pretreatment with PCPA did not reproduce hypoglycemic response to 2 Hz EA in naloxone-treated rats and MOR-KOM mice. Furthermore, injection of serotonin decreased the plasma glucose levels significantly. Therefore, we suggest that serotonin also involved in the hypoglycemic action of 2 Hz EA at both zusanli acupoints of normal rats.

Acupuncture Points↗

PubMed2005

Mechanism of the hypoglycemic effect of stevioside, a glycoside of Stevia rebaudiana.

We have studied the effects of stevioside on the glucose and insulin metabolism in 2 models of diabetes in rats, STZ-induced diabetic rats and NIDDM diabetic rats induced by feeding with fructose. Stevioside (0.5 mg/kg), lowered the blood glucose levels in STZ-induced diabetic rats, peaking at 90 min. Stevioside administered twice daily also demonstrated dose-dependent effects in lowering the glucose levels in both diabetic rat models. Stevioside reduced the rise in glucose during glucose tolerance testing in normal rats. Stevioside dose-dependently decreased protein levels of phosphoenol pyruvate carboxykinase (PEPCK) and PEPCK mRNA after 15 days of treatment. Stevioside also reduced insulin resistance in the diabetic animals as shown by the glucose lowering effects of tolbutamide. In conclusion, stevioside was able to regulate blood glucose levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats; the latter was due to decreased PEPCK gene expression in rat liver by stevioside's action of slowing down gluconeogenesis. Further studies of this agent for the treatment of diabetes appear warranted.

Animals↗

PubMed2005

Myricetin as the active principle of Abelmoschus moschatus to lower plasma glucose in streptozotocin-induced diabetic rats.

The antihyperglycemic action of myricetin, purified from the aerial part of Abelmoschus moschatus (Malvaceae), was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats). Bolus intravenous injection of myricetin decreased the plasma glucose concentrations in a dose-dependent manner in STZ-diabetic rats. Myricetin at the effective dose (1.0 mg/kg) significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. A stimulatory effect of myricetin on glucose uptake of the soleus muscles isolated from STZ-diabetic rats was obtained in a concentration-dependent manner from 0.01 to 10.0 micromol/L. The increase of glucose utilization by myricetin was further characterized using the enhancement of glycogen synthesis in isolated hepatocytes of STZ-diabetic rats. These results suggest that myricetin has an ability to enhance glucose utilization to lower plasma glucose in diabetic rats lacking insulin.

Abelmoschus↗

PubMed2005

Improvement of insulin resistance by Acanthopanax senticosus root in fructose-rich chow-fed rats.

1. In an attempt to develop new substances for handling insulin resistance, an aqueous extract of the root of Acanthopanax senticosus (Araliaceae) was used to screen the effect on insulin resistance induced by fructose-rich chow in rats. 2. Insulin action on glucose disposal rate was measured using the glucose-insulin index, the product from areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. In addition to the modification of feeding behaviour and a marked decrease in bodyweight, oral administration (three times daily for 3 days) of the aqueous extract of A. senticosus root to rats that had received fructose-rich chow for 4 weeks reversed the elevated value of the glucose--insulin index, indicating that this herb has the ability to improve insulin sensitivity. 3. Time for the loss of the plasma glucose-lowering response to tolbutamide (10.0 mg/kg, i.p.) in fructose-rich chow-fed rats was markedly delayed by repeated treatment with the aqueous extract of A. senticosus root compared with the vehicle (saline) -treated group. Thus, an improving effect of A. senticosus root on insulin resistance can be considered. 4. An increase in insulin sensitivity following the administration of this herb was further identified using the plasma glucose-lowering action of exogenous insulin in streptozotocin (STZ)-diabetic rats. Oral administration of the aqueous extract of A. senticosus root at a dose of 150.0 mg/kg three times daily to STZ-diabetic rats increased the responses to exogenous insulin 10 days later. 5. The results obtained suggest that oral administration of the aqueous extract from A. senticosus root has the ability to improve insulin sensitivity and delay the development of insulin resistance in rats and, thus, may be used as an adjuvant therapy for patients with insulin resistance.

Animals↗

PubMed2005

Changes in bladder nerve-growth factor and p75 genetic expression in streptozotocin-induced diabetic rats.

OBJECTIVE: To assess changes associated with diabetes in urinary bladder nerve-growth factor (NGF) and NGF receptor p75NTR expression using a streptozotocin (STZ)-induced diabetic rat model. MATERIALS AND METHODS: Male Wistar rats (32) were divided into four equal groups: group I, vehicle-treated normal rats; group II, vehicle-treated 9-week STZ-diabetic rats; group III, insulin-treated 9-week STZ-diabetic rats; group IV, phlorizin-treated 9-week STZ-diabetic rats. Bladder NGF levels were measured by enzyme-linked immunosorbent assay. Expressions of the mRNAs that encoded NGF and NGF receptor p75NTR in the rat bladder were evaluated using reverse transcription-polymerase chain reaction. RESULTS: The mean (SEM) NGF level in the STZ-diabetic rat bladder was significantly lower than in the control group, at 56.56 (8.28) and 84.33 (11.05) pg/microg protein, respectively (P < 0.01). The mRNA expressions of bladder NGF and p75NTR in the diabetic rats were significantly lower than in the control group (P < 0.05 and <0.001, respectively). Treatment with either insulin or phlorizin restored the normal blood sugar level; moreover, the bladder NGF levels and the expressions of both NGF and p75NTR mRNAs were normal. CONCLUSION: The decrease in the genetic expression of NGF and p75NTR might be responsible for the pathogenesis of diabetic cystopathy while hyperglycaemia is part of the cause of these changes.

Animals↗

PubMed2004

Inhibitory effect of buflomedil on prostate alpha1A adrenoceptor in the Wistar rat.

The inhibitory effect of buflomedil on alpha1A-adrenoceptor (AR) in the prostate of Wistar rat was investigated in this study. Normotensive and spontaneous hypertensive rats were orally fed with buflomedil (150 mg/kg). The drug effects on blood pressure and heart rate were monitored by photoelectric volume oscillometric method. Prostate tissue strips from normotensive rats were contracted in vitro in organ bath by phenylephrine (10(-8) to 10(-2)M). The inhibitory effects of buflomedil (10(-9) to 10(-7)M) on the phenylephrine-induced contractions were measured. Radioligand binding displacement study by buflomedil was performed on rat prostate alpha1A-adrenoceptor (AR) and spleen alpha1B-AR. Furthermore the effects of buflomedil and WB-4101 on phenylephrine (10 microM) activated uptake of 2-[14C]-deoxy-d-glucose (2-DG) into C2C12 cells were evaluated. The results showed that buflomedil feeding did not alter the systolic blood pressure of either spontaneous hypertensive rats or normal rats. Dose-inhibition curves of phenylephrine-induced prostate contraction demonstrated a higher potency of buflomedil than tamsulosin. Buflomedil displaced [3H]prazosin binding in a concentration-dependent manner both in rat prostate alpha1A-AR and spleen alpha1B-AR. The ratio of affinity to alpha1A-AR and alpha1B-AR for buflomedil was 4.06/6.84, indicating selectivity on alpha1A-AR over alpha1B-AR. Activation of C2C12 cell alpha1A-AR by phenylephrine increased the glucose uptake to 116%. Both buflomedil and WB-4101 inhibited the uptake in a concentration-dependent manner. In conclusion, the findings showed that buflomedil has preferential alpha1A-AR antagonistic effect to inhibit prostate contraction without significantly affecting the blood pressure.

Adrenergic alpha-Agonists↗

PubMed2004

Mediation of Endogenous beta-endorphin by Tetrandrine to Lower Plasma Glucose in Streptozotocin-induced Diabetic Rats.

The role of beta-endorphin in the plasma glucose-lowering action of tetrandrine in streptozotocin-induced diabetic rats (STZ-diabetic rats) was investigated. The plasma glucose concentration was assessed by the glucose oxidase method. The enzyme-linked immunosorbent assay was used to determine the plasma level of beta-endorphin-like immunoreactivity (BER). The mRNA levels of glucose transporter subtype 4 (GLUT4) in soleus muscle and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of STZ-diabetic rats were detected by Northern blotting analysis. The expressed protein of GLUT4 or PEPCK was characterized by Western blotting analysis. Tetrandrine dose-dependently increased plasma BER in a manner parallel to the decrease of plasma glucose in STZ-diabetic rats. Moreover, the plasma glucose-lowering effect of tetrandrine was inhibited by naloxone and naloxonazine at doses sufficient to block opioid μ-receptors. Further, tetrandrine failed to produce plasma glucose-lowering action in opioid μ-receptor knockout diabetic mice. Bilateral adrenalectomy eliminated the plasma glucose-lowering effect and plasma BER-elevating effect of tetrandrine in STZ-diabetic rats. Both effects were abolished by treatment with hexamethonium or pentolinium at doses sufficient to block nicotinic receptors. Tetrandrine enhanced BER release directly from the isolated adrenal medulla of STZ-diabetic rats and this action was abolished by the blockade of nicotinic receptors. Repeated intravenous administration of tetrandrine (1.0 mg/kg) to STZ-diabetic rats for 3 days resulted in an increase in the mRNA and protein levels of the GLUT4 in soleus muscle, in addition to the lowering of plasma glucose. Similar treatment with tetrandrine reversed the elevated mRNA and protein levels of PEPCK in the liver of STZ-diabetic rats. The obtained results suggest that tetrandrine may induce the activation of nicotinic receptors in adrenal medulla to enhance the secretion of beta-endorphin, which could stimulate opioid μ-receptors to increase glucose utilization or/and reduce hepatic gluconeogenesis to lower plasma glucose levels in STZ-diabetic rats.

Journal Article↗

PubMed2004

Multiple sources of endogenous opioid peptide involved in the hypoglycemic response to 15 Hz electroacupuncture at the Zhongwan acupoint in rats.

A decrease in plasma glucose levels was observed in rats which received electroacupuncture (EA) stimulation at the Zhongwan acupoint. In the present study, the role of the adrenal gland in this hypoglycemic response to EA at high frequency (15 Hz) was investigated on adrenalectomized (ADX) normal rats. There was a sharper decrease in plasma glucose by EA stimulation in the fasting ADX group than in the fasting sham-operated group. Naloxone blocked this hypoglycemic response to EA stimulation in rats which received ADX. Stimulation of EA failed to elicit an increase in plasma beta-endorphin and insulin levels in ADX rats. Similar results were observed in sham and ADX mice. EA stimulation of ADX mice can reduce plasma glucose levels. Furthermore, naloxone abolished the hypoglycemic response to EA stimulation in mice. Such a hypoglycemic response to EA stimulation was also observed in micro-opioid receptor knockout mice (MOR-KOM). Mediation by another opioid peptide should also be considered in future experiments. We conclude that multiple sources of endogenous opioid peptide participated in the lowering of plasma glucose in rats induced by EA stimulation at higher frequency (15 Hz) at the Zhongwan acupoint. Increase in beta-endorphin levels from the adrenal gland enhances the secretion of insulin, there by reducing plasma glucose levels, and is partially involved in this EA stimulation.

Acupuncture Points↗

PubMed2004

Isosteviol acts on potassium channels to relax isolated aortic strips of Wistar rat.

Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil. In the present study, the role of potassium channels in the vasodilator effect of isosteviol was investigated using potassium channel blockers on isosteviol-induced relaxation of isolated aortic rings prepared from Wistar rats. Isosteviol dose-dependently relaxed the vasopressin (10(-8) M)-induced vasoconstriction in isolated aortic rings with or without endothelium. However, in the presence of potassium chloride (3x10(-2) M), the vasodilator effect of isosteviol on arterial strips disappeared. Only the inhibitors specific for the ATP-sensitive potassium (K(ATP)) channel or small conductance calcium-activated potassium (SK(Ca)) channel inhibited the vasodilator effect of isosteviol in isolated aortic rings contracted with 10(-8) M vasopressin. Also; since the isosteviol-induced relaxation was unchanged by methylene blue, a role of nitric oxide and/or endothelium in the vasodilatation produced by isosteviol could be ruled out. The obtained results indicated that vasodilatation induced by isosteviol is related to the opening of SK(Ca) and K(ATP) channels.

Animals↗

PubMed2004

Activation of imidazoline receptor by agmatine to lower plasma glucose in streptozotocin-induced diabetic rats.

In the present study, we use agmatine, an endogenous ligand, to investigate the role of imidazoline receptor in plasma glucose regulation in streptozotocin-induced diabetic rats (STZ-diabetic rats). After injection into the central lateral ventral (i.c.v.) of fasting STZ-diabetic rats for 30 min, agmatine produced plasma glucose lowering action in a concentration-dependent manner without alteration the mean arterial pressure (MAP). However, the plasma glucose was markedly raised in STZ-diabetic rats receiving similar injection of clonidine at dose (1 micromol/rat, i.c.v.) sufficient to lower MAP. Mediation of alpha(2)-adrenoceptor in this action of agmatine seems unlikely. The plasma glucose lowering action of agmatine (1 micromol/rat, i.c.v.) was abolished by the pretreatment with BU-224 at concentration (100 nmol/rat) sufficient to block cerebral I(2)-imidazoline receptors. Also, this action of agmatine in STZ-diabetic rats disappeared by spinal cord truncation between C6 and C7. Activation of cerebral I(2)-imidazoline receptor by agmatine can thus be considered for the lowering of plasma glucose. In conclusion, we suggest that an activation of I(2)-imidazoline receptors in the brain may lower plasma glucose without insulin in animal.

Agmatine↗

PubMed2004

Isosteviol as a potassium channel opener to lower intracellular calcium concentrations in cultured aortic smooth muscle cells.

Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, and is commonly used as a non-caloric sugar substitute in Japan and Brazil. The present study attempted to elucidate the role of potassium (K (+)) channels in the action of isosteviol on intracellular calcium concentrations ([Ca (2+)]i) in cultured vascular smooth muscle (A7r5) cells using the Ca (2+)-sensitive dye Fura-2 as an indicator. The increase of [Ca (2+)]i in A7r5 cells produced by vasopressin (1 micromol/L) or phenylephrine (1 micromol/L) was attenuated by isosteviol from 0.01 micromol/L to 10 micromol/L. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca (2+)]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca (2+)]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present. Therefore, not only did the ATP-sensitive potassium (K (ATP)) channel affect the action of isosteviol on [Ca (2+)]i modulation in A7r5 cells, but also those on the small conductance calcium-activated potassium (SK (Ca)) channels and voltage-gated (Kv) channels. However, the blockers of large-conductance Ca (2+)-activated potassium channels failed to modify the inhibitory action of isosteviol on [Ca (2+)]i. The obtained results indicated that a decrease of [Ca (2+)]i in A7r5 cells by isosteviol is mainly mediated by the selective opening of K (ATP) channel or/and SK (Ca) channel. Alteration in the Kv channel also plays a critical role in the inhibitory action of isosteviol.

Animals↗

PubMed2004

Mediation of beta-endorphin by the isoflavone puerarin to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigate the mechanism(s) of plasma glucose lowering action of puerarin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Puerarin at the effective dosage to lower higher plasma glucose increased plasma beta-endorphin-like immunoreactivity (BER) in STZ-diabetic rats. Both effects of puerarin were abolished by the pretreatment with prazosin. Also, puerarin enhanced BER release from isolated rat adrenal medulla in a concentration-dependent manner that can be abolished by prazosin. Moreover, bilateral adrenalectomy in STZ-diabetic rats eliminated the actions of puerarin including the plasma glucose lowering effect and plasma BER elevating effect. In addition, naloxone and naloxonazine inhibited the plasma glucose lowering action of puerarin. Unlike in wild-type diabetic mice, puerarin failed to lower the plasma glucose in opioid micro-receptor knockout diabetic mice. In conclusion, our results suggest that puerarin may activate alpha (1)-adrenoceptors on the adrenal gland to enhance the secretion of beta-endorphin to result in a decrease of plasma glucose in STZ-diabetic rats.

Animals↗

PubMed2004

Hydroxylation and glucosidation of ent-16beta-Hydroxybeyeran-19-oic acid by Bacillus megaterium and Aspergillus niger.

ent-16beta-Hydroxybeyeran-19-oic acid ( 1) has potential antihypertensive activity. To obtain novel and more-effective compounds, 1 was incubated with Bacillus megaterium ATCC 14 581 and Aspergillus niger CCRC 32 720. The structures of the metabolites were determined by HR-FAB-MS, 1D- and 2D-NMR spectral data, and enzymatic hydrolysis. Bacillus megaterium hydroxylated and glucosidated 1 to yield ent-7alpha,16beta-dihydroxybeyeran-19-oic acid ( 2), ent-16beta-hydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 3), and ent-7alpha,16beta-dihydroxybeyeran-19-oic acid alpha- D-glucopyranosyl ester ( 4). Aspergillus niger hydroxylated 1 to yield ent-1beta,7alpha,16beta-trihydroxybeyeran-19-oic acid ( 5) and ent-1beta,7alpha-dihydroxy-16-oxobeyeran-19-oic acid ( 6). Metabolites 3 - 5 were characterized as new compounds. In addition, 2, 3, 5, and 6 were tested for antihypertensive effects, and we found that 5 and 6 were more potent than the parent compound 1.

Antihypertensive Agents↗

PubMed2004

Activation of alpha1A-adrenoceptors by genistein at concentrations lower than that to inhibit tyrosine kinase in cultured C2C12 cells.

Genistein, an isoflavonoid natural product, is widely used to inhibit protein tyrosine kinase (PTK). In the present study, we investigated the possible influence of genistein on alpha (1)-adrenoceptors (AR) in cultured C2C12 cells. Genistein enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner. Similar results were also observed in samples treated with daidzein, the inactive congener for PTK inhibition. The effect of genistein on alpha (1)-AR was further characterized using the displacement of [ (3)H]prazosin binding in C2C12 cells. The increase in radioactive glucose uptake by genistein was abolished by RS17053 at a concentration sufficient to block alpha (1A)-AR. The pharmacological inhibition of phospholipase C (PLC) by U73122 resulted in a concentration-dependent reduction of genistein-stimulated glucose uptake in C2C12 cells. This inhibition by U73122 was specific because the inactive congener, U73343, failed to modify the action of genistein. Moreover, genistein can activate alpha (1A)-AR at a concentration (1 micromol/L) lower than that (50 micromol/L) needed to abolish the insulin-stimulated phosphorylation of PTK. The obtained data indicate an activation of alpha (1A)-AR by genistein to increase the glucose uptake into C2C12 cells and this supports the application of genistein as a TK inhibitor.

Adrenergic alpha-Antagonists↗

PubMed2004

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.

Adrenergic alpha-Antagonists↗