Biomedical subjects

Juei-Tang Cheng

Publications and source records attributed to Juei-Tang Cheng.

At least 19 recordsLinked to original sources

PubMed2007

Microbial metabolism of steviol and steviol-16alpha,17-epoxide.

Steviol (2) possesses a blood glucose-lowering property. In order to produce potentially more- or less-active, toxic, or inactive metabolites compared to steviol (2), its microbial metabolism was investigated. Incubation of 2 with the microorganisms Bacillus megaterium ATCC 14581, Mucor recurvatus MR 36, and Aspergillus niger BCRC 32720 yielded one new metabolite, ent-7alpha,11beta,13-trihydroxykaur-16-en-19-oic acid (7), together with four known related biotransformation products, ent-7alpha,13-dihydroxykaur-16-en-19-oic acid (3), ent-13-hydroxykaur-16-en-19-alpha-d-glucopyranosyl ester (4), ent-13,16beta,17-trihydroxykauran-19-oic acid (5), and ent-13-hydroxy-7-ketokaur-16-en-19-oic acid (6). The preliminary testing of antihyperglycemic effects showed that 5 was more potent than the parent compound (2). Thus, the microbial metabolism of steviol-16alpha,17-epoxide (8) with M. recurvatus MR 36 was continued to produce higher amounts of 5 for future study of its action mechanism. Preparative-scale fermentation of 8 yielded 5, ent-11alpha,13,16alpha,17-tetrahydroxykauran-19-oic acid (10), ent-1beta,17-dihydroxy-16-ketobeyeran-19-oic acid (11), and ent-7alpha,17-dihydroxy-16-ketobeyeran-19-oic acid (13), together with three new metabolites: ent-13,16beta-dihydroxykauran-17-acetoxy-19-oic acid (9), ent-11beta,13-dihydroxy-16beta,17-epoxykauran-19-oic acid (12), and ent-11beta,13,16beta,17-tetrahydroxykauran-19-oic acid (14). The structures of the compounds were fully elucidated using 1D and 2D NMR spectroscopic techniques, as well as HRFABMS. In addition, a GRE (glucocorticoid responsive element)-mediated luciferase reporter assay was used to initially screen the compounds 3-5, and 7 as glucocorticoid agonists. Compounds 4, 5 and 7 showed significant effects.

Aspergillus niger↗

PubMed2006

Increase of acetylcholine release by Panax ginseng root enhances insulin secretion in Wistar rats.

The present study was designed to ascertain the effect of Panax ginseng root on plasma glucose and investigate the possible mechanisms for the effect. Ninety minutes after the oral administration of P. ginseng root to fasting Wistar rats, plasma glucose decreased in a dose-dependent manner. Simultaneous with the reduction in plasma glucose, an increase in the plasma level of insulin and C-peptide was also observed. Moreover, disruption of the available synaptic acetylcholine (ACh), using the inhibitor for choline uptake (hemicholinium-3), or the inhibitor for vesicular choline transport (vesamicol), abolished the metabolic actions of P. ginseng root. Conversely, physostigmine, at a concentration sufficient to inhibit acetylcholinesterase, enhanced the metabolic effect of P. ginseng root. It is possible that P. ginseng root mediates the release of ACh from nerve terminals to enhance insulin secretion. Blockade of the actions of P. ginseng root by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP) suggested that the site of action is the muscarinic M(3) receptor. Taken together, the results suggest that P. ginseng root has the ability to increase the release of ACh from nerve terminals in rats so as to stimulate muscarinic M(3) receptors activity located in the pancreatic cells for the secretion of insulin, which in turn lower plasma glucose.

Acetylcholine↗

PubMed2006

Alterations of M(2)-muscarinic receptor protein and mRNA expression in the urothelium and muscle layer of the streptozotocin-induced diabetic rat urinary bladder.

Diabetes associated alterations of M2-muscarinic receptors (M2-mAChR) in the urothelium and muscle layer of the urinary bladder were studied using streptozotocin (STZ)-induced diabetic rats. Male Wistar rats were divided into two groups; group I: normal control rats; group II: STZ-induced diabetic rats, 2 weeks after induction. The bladder was divided into urothelium and muscle layer by microdissection. Tissue M2-mAChR protein levels were measured by Western blotting. Expression of the mRNA that encoded M2-mAChR was estimated using the method of reverse transcription combined with polymerase chain reaction (RT-PCR). M2-mAChR protein and mRNA expressions were found in both the urothelium and muscle layer of the rat urinary bladder. In control rats, the M2-mAChR protein expression ratio in the urothelium and muscle layer was 1:1.66; that for mRNA was 1:0.97. Two weeks after induction of diabetes, the M2-mAChR mRNA expression in the urothelium and muscle layer were significantly increased by 44.4% (P<0.01, n=8) and 28.6% (P<0.01, n=8), respectively. Correspondently, the bladder M2-mAChR protein levels were significantly increased by 33.3% (P<0.001, n=8) in the urothelium and 25.3% (P<0.01, n=8) in the muscle layer of the diabetic rats. In conclusion, M2-mAChR mRNA and protein are expressed in both the urothelium and muscle layer of the rat urinary bladder. STZ-induced diabetes increases mRNA and protein expression of the M2-mAChR in the urothelium as well as the muscle layer.

Animals↗

PubMed2006

Chronic fluoxetine administration desensitizes the hyperglycemia but not the anorexia induced by serotonin in rats receiving fructose-enriched chow.

The present study examined the effect of chronic fluoxetine administration on the feeding behavior of fructose-fed rats. Male fructose-fed rats were divided into two groups: (1) control fructose-fed rats (CFR), and (2) fructose-fed rats treated with oral fluoxetine 5 mg/kg/day for 30 days (FFR). The feeding behaviors and plasma glucose levels in response to either serotonin (5-HT, 5 mg/kg) or saline injection were studied. The results showed 5-HT increased CFR plasma glucose in a dose-dependent fashion while FFR demonstrated significantly lower responses to 5-HT stimulation. 5-HT significantly increased the feeding latency and decreased the amount of food intake in the CFR. Fluoxetine treatment did not affect the 5-HT effect on food intake amount but significantly reduced the 5-HT effect on feeding latency. Putting the animals in a new environment increased the 5-HT effect on feeding latency further; the effect was ameliorated in the FFR. In conclusion, 5-HT induced hyperglycemia, increased feeding latency and decreased food intake amount in fructose-fed rats. Chronic administration of fluoxetine counteracted the 5-HT effects on blood glucose level and feeding latency, but not on the amount of food intake.

Animal Feed↗

PubMed2006

Release of acetylcholine to raise insulin secretion in Wistar rats by oleanolic acid, one of the active principles contained in Cornus officinalis.

The plasma glucose lowering action of fruits of cornus (Cornus officinalis), the major active constituent of Die-Huang-Wan, has been documented to mediate acetylcholine (ACh) release, which in turn to stimulate muscarinic M(3) receptors resulting in the enhancement of insulin secretion in rats with functional pancreatic beta-cells. The present study was conducted to investigate the effect of oleanolic acid, one of the active principles of cornus fruit, on the release of insulin in rats. After an intraperitoneal injection into the fasting Wistar rats for 90 min, oleanolic acid decreased the plasma glucose in a dose-dependent manner in parallel to an increase of plasma levels of insulin as well as C-peptide. Moreover, disruption of synaptic ACh using an inhibitor of choline uptake, hemicholinium-3, or vesicular acetylcholine transport, vesamicol, abolished these actions of oleanolic acid. Also, physostigmine at concentration sufficient to inhibit acetylcholinesterase enhanced the actions of oleanolic acid. Both the plasma glucose lowering action and the raised plasma levels of insulin and C-peptide induced by oleanolic acid were also inhibited by 4-diphenylacetoxy-N-methylpiperdine methiodide (4-DAMP), but not affected by the ganglionic nicotinic antagonist, pentolinium or hexamethonium. The results suggest that oleanolic acid has an ability to raise the release of ACh from nerve terminals, which in turn to stimulate muscarinic M(3) receptors in the pancreatic cells and augment the insulin release to result in plasma glucose lowering action. Thus, oleanolic acid is one of the active principles responsible for the increase of plasma insulin produced by cornus fruit in rats.

Acetylcholine↗

PubMed2006

Enhanced insulin sensitivity using electroacupuncture on bilateral Zusanli acupoints (ST 36) in rats.

In this study, intravenous glucose tolerance test (ivGTT) and insulin challenge test (ICT) were applied to evaluate the influence of electroacupuncture (EA) on insulin sensitivity in rats. Firstly, hypoglycemic activity was confirmed on normal Wistar rats (36+/-12%) and streptozotocin (STZ)-induced diabetic rats (13+/-8%) after 60 min of 15 Hz EA on bilateral Zusanli acupoints. The rats were divided into the experiment group (EG) and control group (CG) randomly. After fasting, plasma glucose and insulin levels were assayed in the normal Wistar rats undergoing ivGTT. Plasma glucose levels and hypoglycemic activity were also evaluated in the normal Wistar rats and STZ diabetic rats during ICT. As the data showed, EA improved the glucose tolerance from 15 to 90 min (p<0.005 compared with the plasma glucose levels of the CG) during ivGTT. In addition, significant improvement in the Homeostasis Model Assessment (HOMA) index was found in the EG from 15 to 90 min (p<0.005 compared with the CG). More hypoglycemic activity was achieved in normal Wistar and STZ diabetic rats in the EG than in the CG (from 30 to 60 min) during ICT. In conclusion, the results suggest that 15 Hz EA at bilateral Zusanli acupoints improved glucose tolerance. Thus, EA should be considered as an alternative method for improving insulin sensitivity and/or increase insulin-hypoglycemic activity in rats.

Acupuncture Points↗

PubMed2006

The antihypertensive activity of angiotensin-converting enzyme inhibitory peptide containing in bovine lactoferrin.

Angiotensin I-converting enzyme (ACE) inhibitory peptide was isolated from the bovine lactoferrin hydrolysate using peptic hydrolysis by 2-step of reverse-phase high-performance liquid chromatography. This peptide was identified as Leu-Arg-Pro-Val-Ala-Ala and it produced a concentration-dependent inhibition of ACE activity in vitro with an IC50 value of about 4.14 microM. Also, this inhibition was identified as noncompetitive from the Lineweaver-Burk plot. Moreover, the antihypertensive activity of Leu-Arg-Pro-Val-Ala-Ala was investigated by the intravenous injection into spontaneously hypertensive rats (SHRs). A dose-dependent reduction of systolic blood pressure by this peptide was observed at 60 min after injection and it maximally decreased the blood pressure at a rate of 1 nmol/ml/kg. The blood pressure lowering activity of this peptide was calculated as 210% of captopril (10 pmol/ml/kg) that was used as positive control. Otherwise, identification of this peptide in the blood of SHRs was carried out chromatographically. Reduction of blood pressure coincides with the peak peptide concentration in the serum. Thus, we conclude that this peptide inhibits ACE activity in vitro and lowers systolic blood pressure in spontaneously hypertensive rat.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2006

Increase of adiponectin receptor gene expression by physical exercise in soleus muscle of obese Zucker rats.

Aerobic exercise, including treadmill running has been widely used to treat insulin resistance and type 2 diabetes. We studied the effects of endurance training on gene expression of adiponectin receptor 1 (AdipoR1) in skeletal muscle of obese Zucker rats: the 8-week moderate exercise program consisted of treadmill running at 20 m/min and 0 degrees gradient for 1 h/day, 7 days/week. After 8 weeks, insulin action on glucose disposal rate was measured by glucose-insulin index, the product of the areas under the curve of glucose and insulin during intraperitoneal glucose tolerance testing. In contrast to results for sedentary obese rats, exercise training decreased plasma levels of insulin and glucose as well as the glucose-insulin index in obese rats, indicating the merit of regular moderate exercise for improvement of insulin sensitivity in this insulin-resistant animal model. Also, diabetes-related reductions in mRNA and protein content of AdipoR1 in soleus muscle were observed in obese rats at baseline; they were markedly reversed after the 8-week exercise program. However, such exercise training did not alter plasma levels of insulin and glucose in lean Zucker rats. Also, AdipoR1 gene expression in soleus muscle was not changed by exercise in lean Zucker rats compared with the sedentary, lean littermates. These results suggest that long-term exercise training may reverse reduced AdipoR1 gene expression in soleus muscle and improve insulin sensitivity in the obese Zucker rats. Thus, an endurance exercise training is probably helpful clinically for obese individuals with insulin resistance.

Animals↗

PubMed2006

Merit of physical exercise to reverse the higher gene expression of hepatic phosphoenolpyruvate carboxykinase in obese Zucker rats.

Effects of endurance training on the phosphoenolpyruvate carboxykinase (PEPCK), a rate-limiting enzyme of gluconeogenesis, were studied in the obese Zucker rats. We used a moderate exercise program consisting of treadmill running at 20 m/min and 0-degree gradient for 1 h/day, 7 days/week, for 8 weeks. At the end of the experimental period, insulin action on glucose disposal rate was measured using the glucose-insulin index, the product of the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. Furthermore, changes of hepatic PEPCK gene expression were detected using reverse transcriptase polymerase chain reaction to assay the mRNA level and Western blot analysis to detect the protein level. Different to sedentary obese rats, an elevation in the value of glucose-insulin index from the exercised obese rats declined, indicating the marked effect of regular moderate exercise on the improvement of insulin sensitivity in this insulin resistant animal model. Moreover, the diabetes-related elevation in mRNA level and protein content of hepatic PEPCK were observed in non-exercise obese groups but they were markedly reduced by exercise training. In addition, chronic exercise training enhanced the insulin sensitivity of lean Zucker rats, since the value of glucose-insulin index was lower than that of untrained lean groups. Also, the hepatic PEPCK gene expressions both the mRNA and protein levels were reduced in exercised lean Zucker rats as compared with their sedentary littermates. These results suggest that modulation of hepatic PEPCK gene expression by chronic exercise training might be related to the enhancement of insulin sensitivity. Thus, endurance exercise training could aid in the prevention and/or treatment of individuals with insulin resistance.

Animals↗

PubMed2006

Increase of peroxisome proliferator-activated receptor delta gene expression in the lungs of streptozotocin-induced diabetic rats.

Peroxisome proliferator-activated receptors (PPARs) play key roles in the regulation of energy homeostasis and inflammation while the agonists of PPARalpha and PPARgamma are recently used for therapy in clinic. However, functions of PPARdelta are still unclear. In the present study, we investigated the changes of PPARdelta gene expression in the lung of diabetic rats. The mean level of mRNA transcripts encoding PPARdelta was increased in the lung isolated from streptozotocin-induced diabetic rats (STZ-diabetic rats) to about 1.6-fold of that in normal rats. Exogenous insulin at the dose sufficient to normalize the plasma glucose of STZ-diabetic rats reversed the mRNA level of PPARdelta in lungs after a 4-day treatment. Similar results were also observed in STZ-diabetic rats that received the treatment of phlorizin to reverse the plasma glucose level for 4 days. Otherwise, the protein level of PPARdelta was higher in the lung of STZ-diabetic rats than that in normal rats. Treatment with exogenous insulin or phlorizin reversed this elevated protein level of PPARdelta in the lung of STZ-diabetic rats to near the normal level. The obtained results suggest that increase of plasma glucose is responsible for the higher gene expression of PPARdelta in the lung of STZ-diabetic rats.

Animals↗

PubMed2006

Effect of opioid mu-receptors activation on insulin signals damaged by tumor necrosis factor alpha in myoblast C2C12 cells.

In an attempt to develop a new target for handling of insulin resistance, we investigated the effect of opioid mu-receptor activation on insulin signals in differentiated myoblast C2C12 cells damaged by tumor necrosis factor-alpha (TNFalpha). A marked reduction of insulin-stimulated radioactive 2-deoxyglucose (2-DG) uptake was observed in TNFalpha (10 ng/ml for 1 h)-treated cells. Loperamide (10 micromol/l for 24 h) reversed the inhibition of insulin-stimulated 2-DG uptake by TNFalpha in a manner sensitive to blockade of opioid mu-receptors. Insulin signals damaged by TNFalpha were the impaired expressions of insulin receptor (IR), tyrosine autophosphorylation in IR, and insulin receptor substrate (IRS)-1 protein, as well as a decrease of IRS-1 tyrosine phosphorylation. Also, the signaling defects including an attenuated p85 regulatory subunit of phosphatidylinositol 3-kinase (PI3-kinase) and Akt serine phosphorylation were observed. Loperamide (10 micromol/l for 24 h) reversed the TNFalpha-induced decrement of insulin signals at same concentration used to raise glucose uptake. In conclusion, activation of opioid mu-receptors may reverse the insulin signals damaged by inflammatory cytokine.

Animals↗

PubMed2006

Improvement of insulin resistance by miracle fruit (Synsepalum dulcificum) in fructose-rich chow-fed rats.

In an attempt to probe a new target to improve insulin resistance, miracle fruit (Synsepalum dulcificum) was employed to investigate the effect on insulin resistance induced by fructose-rich chow in rats. Single oral administration of the powder of this miracle fruit decreased the plasma glucose in a dose-dependent manner for 150 min in rats fed fructose-rich chow for 4 weeks. Insulin action on the glucose disposal rate was measured using the glucose-insulin index, the value of the areas under the curve of glucose and insulin during the intraperitoneal glucose tolerance test. Oral administration of miracle fruit (0.2 mg/kg) to fructose-rich chow fed rats, three times daily for 3 days, reversed the raised value of the glucose-insulin index, indicating that miracle fruit has the ability to improve insulin sensitivity. The plasma glucose lowering action of tolbutamide, induced by secretion of endogenous insulin, is widely used to characterize the formation of insulin resistance. The 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 after treatment with miracle fruit compared with the vehicle-treated group. Thus providing supportive data that oral administration of miracle fruit could delay the development of insulin resistance in rats. Also, the in vivo insulin sensitivity was markedly raised by miracle fruit. In conclusion, the results suggest that miracle fruit may be used as an adjuvant for treating diabetic patients with insulin resistance because this fruit has the ability to improve insulin sensitivity.

Animals↗

PubMed2006

Adjuvant bupivacaine scalp block facilitates stabilization of hemodynamics in patients undergoing craniotomy with general anesthesia: a preliminary report.

STUDY OBJECTIVE: To evaluate the effect of 0.25% bupivacaine scalp block on alterations in hemodynamics and plasma catecholamine metabolites during general anesthesia in patients undergoing frontotemporal craniotomy. DESIGN: Prospective, clinical study. SETTING: Operating room of a university hospital. PATIENTS: 16 ASA physical status II and III patients who were scheduled for frontotemporal craniotomy. INTERVENTIONS: Patients were prospectively randomized to receive a saline control (C group) or bupivacaine scalp block (SB group) as an adjuvant to general anesthesia using isoflurane in 50% N(2)O-O(2). MEASUREMENTS: Routine monitoring of electrocardiogram, heart rate (HR), and mean arterial blood pressure (MAP) were recorded at two-minute intervals from the beginning of anesthesia until 10 minutes after incision, followed by 5-minute intervals throughout the remaining course of the surgery. By prospective design, increases in MAP or HR by 20% above the mean baseline values were treated with 2.5 mg/kg of thiopental combined with 2 mug/kg of fentanyl. Arterial blood was sampled at 5 minutes before and after skin incision and at the start of dural opening for measuring serum catecholamine metabolites by high-performance liquid chromatography. MAIN RESULTS: Only two patients in the SB group needed additional anesthetics for stabilizing their hemodynamics during the course of anesthesia. In contrast, all C group patients required supplemental anesthesia for controlling the abrupt rise in hemodynamic parameters. In addition, absolute MAP and HR values were significantly higher in the C group than in the SB group during the surgical period between incision and dural opening. The differences in hemodynamics observed between the two groups were, however, not accompanied with a significant change in plasma catecholamine metabolites at each predetermined time interval measured. CONCLUSIONS: Pretreatment with 0.25% bupivacaine scalp block appeared to be an effective adjuvant treatment for maintaining stable hemodynamics for patients undergoing craniotomy during general anesthesia especially at the time of skin incision and dural opening. This study design was unable to discern any correlation between elevation in hemodynamic parameters and a rise in serum catecholamine levels.

Adjuvants, Pharmaceutic↗

PubMed2006

Mediation of beta-endorphin by ginsenoside Rh2 to lower plasma glucose in streptozotocin-induced diabetic rats.

We investigated the plasma glucose-lowering mechanism(s) of Rh2, a ginsenoside derived from Panax ginseng, in rats with streptozotocin-induced diabetes (STZ-diabetic rats). After intravenous injection over 120 min into fasting STZ-diabetic rats, Rh2 decreased plasma glucose in a dose-dependent manner. In parallel to the lowering of plasma glucose, an increase of plasma beta-endorphin-like immunoreactivity was observed. In addition, naloxone and naloxonazine at doses sufficient to block opioid mu-receptors inhibited the plasma glucose-lowering action of Rh2 in genetically wild-type, diabetic mice. In contrast, Rh2 failed to lower plasma glucose in opioid mu-receptor knockout diabetic mice. An increase in gene expression at both the mRNA and protein levels of glucose transporter subtype 4 (GLUT 4) was observed in soleus muscle obtained from STZ-diabetic rats treated with Rh2 three times daily for one day; this increase in expression was absent when opioid mu-receptors were blocked. In conclusion, our results suggest that ginsenoside Rh2 may lower plasma glucose in STZ-diabetic rats based on an increase in beta-endorphin secretion that activates opioid mu-receptors thereby resulting in an increased expression of GLUT 4.

Animals↗

PubMed2006

Pumpkin seed oil and phytosterol-F can block testosterone/prazosin-induced prostate growth in rats.

INTRODUCTION: This study was undertaken to investigate the effects of pumpkin seed oil alone or combined with Phytosterol-F on testosterone/prazosin-induced (T-P) prostate growth in rats. MATERIALS AND METHODS: Forty adult Wistar rats were divided into five groups, including: one control group, rats treated with vehicle only, one group treated with T-P, and two groups of T-P-treated rats, one receiving orally pumpkin seed oil alone and one group receiving orally pumpkin seed oil combined with Phytosterol-F. Two weeks later, the prostatic weight-to-body weight ratio was determined after sacrifice. The total protein concentration was measured by using a protein assay. Some ventral prostatic tissues were histologically examined after hematoxylin-eosin staining. RESULTS: Histological sections of the ventral prostate showed that the architecture of the prostate glands became hyperplastic in the T-P rats, but not in the control or vehicle-treated animals. As compared with the control or vehicle group, T-P rats had a significantly higher prostatic weight-to-body weight ratio for the ventral prostate (p=0.05 and p=0.007, respectively), but not for the dorsolateral prostate (p=0.53 and p=0.73, respectively). The T-P rats had significantly higher protein levels within both lobes (ventral lobe, p=0.02 and p<0.0001, respectively; dorsolateral lobe, p=0.06 and p=0.005, respectively). As compared with the T-P-alone rats, the TP rats treated with pumpkin seed oil alone or pumpkin seed oil combined with Phytosterol-F had a significantly lower weight ratio for the ventral prostate (p=0.01 and p=0.004, respectively) and significantly lower protein levels within both lobes (p=0.03 and p=0.003, respectively; p=0.007 and p=0.002, respectively). In addition, Phytosterol-F had some additive effect on the total protein synthesis within the ventral prostate (p=0.02). CONCLUSION: Pumpkin seed oil alone or combined with Phytosterol-F can block the T-P-induced increases in prostatic weight-to-body weight ratio and protein synthesis.

Animals↗

PubMed2006

Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin-induced diabetic rats.

To better understand the insulin-independent plasma glucose-lowering action of metformin, we used streptozotocin (STZ)-induced diabetic rats to investigate the possible mechanisms. Oral intake of metformin decreased the plasma glucose of STZ-induced diabetic rats with a parallel increase of plasma beta-endorphin-like immunoreactivity (BER). Mediation of opioid mu-receptors in the action of metformin was identified by the blockade of receptors with antagonist in STZ-induced diabetic rats and the failure of action in opioid mu-receptor knockout diabetic mice. Release of BER from adrenal glands by metformin was characterized, using bilateral adrenalectomy and the release of BER from isolated adrenal medulla of STZ-induced diabetic rats. Repeated treatment with metformin in STZ-induced diabetic rats increased the mRNA and protein levels of GLUT-4 in soleus muscle that was blocked by naloxonazine. Reduction of the mRNA or protein levels of hepatic PEPCK was also impeded in the same group of STZ-induced diabetic rats. In conclusion, our results provide novel mechanisms for the plasma glucose-lowering action of metformin, via an increase of beta-endorphin secretion from adrenal glands to stimulate opioid mu-receptor linkage, leading to an increase of GLUT-4 gene expression and an attenuation of hepatic PEPCK gene expression in STZ-induced diabetic rats.

Adrenalectomy↗

PubMed2005

Inhibitory effect of 5-hydroxytryptamine on hyperphagia in mice with genetic overexpression of neuropeptide Y.

The present study examined the effect of 5-hydroxytraptamine (5-HT) on the feeding behavior of transgenic mice with neuropeptide Y (NPY) overexpression. Solution of 5-HT (1, 2.5 or 5 mg/kg) was administered intraperitoneally into (1) NPY-overexpressing mice, and (2) wild-type mice with 2-deoxy-d-glucose (2-DG) induced hyperphagia. The NPY-overexpressing mice were further divided into five groups: (1) control mice, (2) mice treated with 5-HT (5 mg/kg), (3) mice treated with 5-HT (5 mg/kg) and ketanserin (0.5 or 1 mg/kg), a 5-HT2A receptor antagonist, (4) mice treated with insulin (1 IU/kg), and (5) mice treated with insulin (1 IU/kg) and 5-HT (5 mg/kg). Food intake and plasma glucose levels were measured. The results showed that 5-HT reduced hyperphagia in both NPY-overexpressing mice and 2-DG-treated mice in dose-dependent manner. Hyperglycemia was induced by 5-HT administration. Ketanserin antagonized the 5-HT induced hypophagia and hyperglycemia. Insulin, on the other hand, prevented 5-HT induced hyperglycemia but not the hypophagic effect. In conclusion, 5-HT reduces hyperphagia in the NPY-overexpressing rat through action on 5-HT2A receptors and this hypophagic effect of 5-HT does not depend on the hyperglycemia.

Animals↗

PubMed2005

Increase of adenosine A1 receptor gene expression in cerebral ischemia of Wistar rats.

In an attempt to know the role of adenosine A1 receptor in cerebral ischemia, the present study employed the ligation of bilateral carotid arteries to induce ischemia in Wistar rats. Changes of gene expression of adenosine A1 receptor in cerebral cortex of ischemic rats were compared with normal sham control and reperfusion group that received regular blood flow after a transient ischemia. The mRNA level of adenosine A1 receptor in cerebral cortex was markedly raised by this artificial ischemia. Also, reperfusion reversed this elevation to a level near the control. This change was also observed at the protein level using Western blot analysis of adenosine A1 receptor. The raised protein level of adenosine A1 receptor by ischemia was reversed to normal level after reperfusion. These data suggest that the gene expression of adenosine A1 receptor was increased by ischemia probably due to the compensative response of brain. The raised adenosine A1 receptor may play a protective role in these damaged tissues.

Adenosine↗