The present study was performed to evaluate the hypoglycemic mechanism of brazilin. Brazilin significantly reduced plasma glucose level in streptozotocin induced diabetie rats and this effect seems to be mediated by extrapancratic effects rather than by pacreatic effect because no significant changes were observed in plasma insulin levels. The rates of glycogen synthesis, glycolysis and glucose oxidation in soleus muscle were markedly increased following brazilin treatment to diabetic animals. Glucose transport seemed to be increased by the treatment of brazilin. Brazilin did not affect insulin binding to muscles from streptozotiocin induced diabetic rats. These results suggest that potentiation of periopheral glucose utilization may be one of the major causes of hypoglucemic action of brazilin.
The present study was conducted to investigate te effect of sea tangle and hypoglycemic agent(Metformin) on lipid peroxidation and antioxidants levels in normal and diabetic rats. Male Sprague-Dawley rats were fed AIN-76 based experimental diets containing 5% (w/w) cellulose or 15%(w/w) sea tangle for 3 weeks, and then rats of diabetic groups were rendered diabetic by intramuscular injection of streptozotocin(STZ, 45mg/kg BW). After induction of diabetes Metformin(350mg/kg BW) was given once a day using a feeding tube for 5 days. Blood glucose level in diabetic rats fed sea tangle was significantly lower than that of diabetic rats fed cellulose. Metformin feeding resulted in further lowering blood glucose. Plasma and liver microsomal levels of lipid peroxides were increased significantly in diabetic rats as compared to normal rats, and the plasma level tended to be decreased by sea tangle feeding. Plasma level of retinol was reduced by STZ treatment, but it was increased by Metformin feeding in diabetic rats fed sea tangle. The liver contents of retinyl plamitate were reduced in diabetic rats but recovered by sea tangle feeding to some extent. Liver contents of total vitamin A were increased significantly by sea tangle in diabetic rats. Although difference in either plasma or liver level of $\alpha$-tocopherol by diet and STZ treatment was not significant, $\alpha$-tocopherol levels were the highest in the group with simultaneous feeding of sea tangle and metformin. Liver contents of zinc and copper were not influenced by either STZ treatment or sea tangle feeding. The present study indicates that the lowering blood glucose level could be attained by simultaneous trial of sea tangle diet and hypoglycemic agent and the increased oxidative stress caused by STZz treatment could be relieved by sea tangle feeding.
This study was carried out to evaluate the effects of fractions of methanol(MeOH) extracts of Lycopus lucidic Turcz on hyperglycemia and energy metabolites in streptozotocin(STZ) diabetic rats. Diabetes mellitus was induced in male Sprague-Dawley rats weighing 200-220 g by an injection of STZ dissolved in a citrate buffer into the tail vein at a dose of 45 mg/kg of body weight, and the rats were divided into 7 groups, that is, one normal group and 6 diabetic groups: STZ-control, hexane, chloroform(CHCl$\sub$3/). ethylacetate(EtOAc), butanol(BuOH) and H$\sub$2/O fraction-fed groups. All groups were fed an AIN-93 diet and the fractions of Lycopus lucidic Turcz were administered orally with 2 % Tween 80 for 14 days after the STZ injection. Body weight, diet intake and organ weights were monitored. The plasma levels of blood glucose, insulin and protein were determined. The plasma concentrations of cholesterol, HDL-cholesterol, triglycerides and free fatty acid were assayed. The plasma activities of aspartate aminotransferase (AST) and alanine aminotransferase(ALT) were also measured. Body weight losses were observed by feeding the fractions of Lycopus lucidic Turcz in STZ experimental groups, and the kidney weight was increased. The extent of blood glucose decrement was significantly greater in the hexane and BuOH fraction-fed groups than STZ-control group. The plasma protein level was significantly lower in the H$\sub$2/O fraction-fed group. The plasma cholesterol level was decreased in BuOH and H$\sub$2/O fraction-fed groups compared with the STZ-control group. The levels of free fatty acids in the CHC1$\sub$3/ and H$\sub$2/O fraction-fed groups were significantly decreased(p<0.05). ALT activitiy of BuOH fraction-fed group was lower than control but it was not significantly different. These results suggest that the fractions of Lycopus lucidic Turcz are capable of lowering blood glucose and fat metabolites concentrations when administered to STZ-treated rats, and AST/ALT activity and insulin levels show the possibility of therapeutic use to diabetes mellitus.
The hypoglycemic effects of five Korean wild vegetables, Aralia continentalis (A. con.), Castanea crenata (C. cre.), Xanthium strumarium (K, str.), Alisma canaliculatum (A. can,) and Eupatorium chinense var. simplicifolium for tripartium (E. tri) which have been utilized for the traditional remedies were investigated in this study. Diabetes mellitus was induced in male Sprague-Dawley rats by injections of streptozotocin (STZ) into the tail veins at a dose of 45 mg/kg. Five groups of STZ-induced diabetic rats were fed one of each experimental diet containing 10% of the Korean wild vegetable powder and normal and STZ-control rats were fed the control diet for five weeks. The body weight change, feed efficiency ratio (FER) and organ weights were compared. The plasma levels of glucose, protein, cholesterol, HDL-cholesterol, triglyceride, free fatty acid, and aminotransferase activity were determined. Mineral (Ca, K, Mg, Na, Cu, Fe, Mn and Zn) contents of the Korean wild vegetables were analyzed. The body weight gain was higher in normal, C. cre., A. can. and E. tri. groups than in the diabetic control group. The FER of C. cre., A. can. and E. tri. groups was significantly higher (p.<0.05) than that of diabetic control group. Liver weight was heavier in A. con., X. str. and A. can. groups compared with the diabetic control group. The weights of kidney were lighter in all five Korean wild vegetable groups than in the diabetic control group. After five weeks, the plasma glucose level tends to be decreased in A. con., A. can. and E. tri. groups. Plasma cholesterol level was decreased the Korean wild vegetables except for X. str. group. Plasma HDL- cholesterol level was significantly higher in A. con., A. can. and E. tri. groups compared with the diabetic control group. Plasma triglyceride and free fatty acid levels were significantly higher in X. str. group compared with the diabetic control group. Mineral contents were higher in E. tri. (Ca, K, Na and Fe). The results suggest that the intakes of A. con., A. can. and E. tri. have a hypoglycemic effect in diabetic rats showing the possibility as the valuable food resources for the prevention of diabetic mellitus.
This study was designed to investigate the anti-diabetic effect and mechanism of Korean red ginseng extract through transcriptomics in C57BL/KsJ db/db mice. The db/db mice were randomly divided into six groups: diabetic control group (DC), red ginseng extract low dose group (RGL, 100 mg/kg), red ginseng extract high dose group (RGH, 200 mg/kg), metformin group (MET, 300 mg/kg), glipizide group (GPZ, 15 mg/kg) and pioglitazone group (PIO, 30 mg/kg), and treated with drugs once per day for 10 weeks. At the end of treatment, we measured blood glucose, insulin, hemoglobin A1c (HbA1c), triglyceride (TG), adiponectin, leptin, non-esterified fatty acid (NEFA). RGL-treated group lowered the blood glucose and HbA1c levels by 19.6% and 11.4% compared to those in diabetic control group. In addition, plasma adiponectin and leptin levels in RGL-treated groups were increased by 20% and 12%, respectively, compared to those in diabetic control. Morphological analyses of liver, pancreas and epidydimal adipose tissue were done by hematoxylin-eosin staining, and pancreatic islet insulin and glucagon levels were detected by double-immunofluorescence staining. RGL-treated group revealed higher insulin contents and lower glucagon contents compared to diabetic control. To elucidate an action mechanism of Korean red ginseng, DNA microarray analyses were performed in liver and fat tissues, and western blot and RT-PCR were conducted in liver for validation. According to hierarchical clustering and principal component analysis of gene expression Korean red ginseng treated groups were close to metformin treated group. In summary, Korean red ginseng lowered the blood glucose level through protecting destruction of islet cells and shifting glucose metabolism from hepatic glucose production to glucose utilization and improving insulin sensitivity through enhancing plasma adiponectin and leptin levels.
This study was carried out to determine whether a short-tenn zinc supplementation contributes to beneficial changes in glycemic control among type 2 diabetic patients. Seventy-six diabetic subjects and 72 normal adults participated in this study. Subjects were divided into supplemented and control groups. Forty-four diabetic patients and 34 normal subjects were supplemented with 50 mg zinc daily as zinc gluconate for 4 weeks. Zinc status was assessed from fasting plasma levels and urinary excretion. The effects of zinc supplementation on fasting blood glucose, $HbA_{1c}$, insulin, and C-peptide were measured at the beginning of the study and after 4 weeks of supplementation. The changes in glycemic control indicators were compared between diabetic groups, classified by baseline $HbA_{1c}$ levels, and by diabetic duration. At baseline, the incidence of marginal zinc deficiency in the diabetic group, as determined by plasma zinc level, was approximately twice as high as in the normal adult group. The changes of $HbA_{1c}$ concentration, and fasting blood glucose following supplementation were not statistically significant in diabetic subjects. In normal subjects, a significant decrease of $HbA_{1c}$ occurred only in the zinc supplemented group. No significant changes were observed for serum insulin and C-peptide in diabetic as well as normal subjects. However, when the changes were compared by baseline $HbA_{1c}$ level, we found that diabetic subjects with $HbA_{1c}\;{\geq}\;7.5%$ showed significantly improved levels of $HbA_{1c}$ and fasting glucose after Zn supplementation. While such improvement in fasting blood glucose was significant among diabetics with shorter diabetic duration, significant levels of increase in serum insulin and C-peptide were observed in zinc supplemented subjects with longer diabetic duration. Fasting blood glucose was significantly decreased, whereas serum insulin and C-peptide were increased in diabetics with marginal zinc status. Therefore, we suggest that Zn supplementation for a short-term period may improve glycemic control in diabetic patients with higher $HbA_{1c}$ levels and marginal zinc status.
Background: Preoperative blocking of surgical nociceptive inputs may prevent sensitization of central nervous system (CNS) and reduce postoperative pain. The stress responses to surgical trauma consist of increase in catabolic hormones and decrease in anabolic hormones. We studied whether preoperative low dose epidural bupivacaine and morphine could affect postoperative pain, changes plasma cortisol, and serum glucose. Methods: Thirty patients undergoing total abdominal hysterectomy were randomly assigned to one of three groups. General anesthesia was induced in all patients and after that, epidural blocks were done except the control group (n=10) patients. Preoperative block group (n=10) received 0.5% bupivacaine 50 mg and morphine 2 mg epidurally as a bolus before operation and followed by 0.1% bupivacaine $5\;mghr^{-1}$ and morphine $0.2\;mghr^{-1}$ for 10 hours. Postoperative block group (n=10) received the same doses of bupivacaine and morphine under the same method postoperatively. Postoperative pain relief was provided with i.v. fentanyl through Patient-Controlled-Analgesia Pump. Postoperative pain by visual analogue scores (VAS), analgesic requirement (first requirement time, total amounts used), side effects, plasma cortisol level and serum glucose level were compared. Results: Until postoperative 6 hrs, VAS of control group was higher than those of the epidural groups. No difference was observed in VAS between the two epidural groups. First analgesics requirement time and total amounts of used analgesics were not different between the two epidural groups, but first analgesic requirement time of preoperative block group was significantly prolonged compared with control group. Plasma cortisol and serum glucose levels were not different among groups. Conclusions: Low dose preoperative epidural bupivacaine and morphine could not reduce postoperative pain, plasma cortisol level and serum glucose level compared with postoperative block group.
To elucidate antidiabetic effect and mechanism(s) of acarbose in a polygenic spontaneous hyperglycemic and hyperinsulinemic diabetic animal model, $KKA^y$ mice, acarbose was administered orally for 4 weeks and effects on body weight, plasma glucose and insulin levels, genetic expressions of intestinal sucrase-isomaltase (SI), sodium-glucose cotransporter (sGLT1) and glucose transporter in quadriceps muscle (GLUT4) were examined in this study. Although no differences in body weight were detected between control and acarbose-treated groups, plasma glucose level in acarbose-treated group was markedly reduced as compared to the control. In the mechanism study, acarbose downregulated the SI and SGLT1 gene expressions, and upregulated the GLUT4 mRNA and protein expressions when compared to the control group. In conclusion, the data obtained strongly implicate that acarbose can prevent the hyperglycemia in $KKA^y$ mice possibly through blocking intestinal glucose absorption by downregulations of SI and sGLT1 mRNA expressions, and upregulation of skeletal muscle GLUT4 mRNA and protein expressions.
The objective of the present study was to investigate the expression of heat shock protein 90 (HSP90) and 70 (HSP70) mRNA as cellular stress responses, the levels of plasma cortisol with glucose as neuro-endocrine stress responses during water temperature rising in freshwater adapted black porgy, Acanthopagrus schlegeli. A cDNA fragment of 891 (HSP90) and 465 (HSP70) bp was cloned from black porgy testis by Reverse transcription-polymerase chain reaction (RT-PCR) with primers designed from the conserved regions of other teleost. The PCR product of HSP90 showed very high homology to red seabream (99%), rainbow trout (95%), Atlantic salmon (94%), zebrafish (94%) HSP90, HSP70 of black porgy was also highly similar to those of rainbow trout (96%), silver seabream (95%), zebrafish (95%) HSP70. Water temperature rising ($20{\sim}30^{\circ}C$) induced elevation of HSP90 mRNA in black porgy gonad, liver, brain, intestine and kidney, whereas it resulted in an induction of the HSP70 mRNA expression in gonad only. Plasma cortisol levels increased significantly at $30^{\circ}C$ in the fish compared to those at $20^{\circ}C$. Glucose levels of the fish showed a tendency of co-increase with cortisol during water temperature rising. These results suggest that increased HSP90 mRNA in liver with plasma cortisol following heat shock may be related to increasing glucose for homeostasis in this species.
Acarviosine-glucose (AcvGlc) is an ${\alpha}$-glucosidase inhibitor and has similar inhibitory activity to acarbose in vitro. We synthesized AcvGlc by treating acarbose with Bacillus stearothermophilus maltogenic amylase and fed C57BL/6J and db/db mice with diets containing purified AcvGlc and acarbose for 1 week. AcvGlc (50 and 100 mg/100 g diet) significantly reduced plasma glucose and triglyceride levels in db/db mice by 42 and 51 %, respectively (p<0.0001). The hypoglycemic and hypotriglyceridemic effects of AcvGlc were slightly, but significantly, greater than those seen with acarbose treatment (p<0.0001) in C57BL/6J mice. In an oral glucose tolerance test, glucose tolerance was significantly improved at all time points (p<0.01). The expression of two novel glucose transporters (GLUTs), GLUT10 and GLUT12, were examined by Western blot analysis. GLUT10 was markedly increased in the db/db livers. After AcvGlc treatment, the expression of hepatic GLUT10 was decreased whereas intestinal GLUT12 was significantly increased in both strains of mice. Our results show that AcvGlc improves plasma lipid and glucose metabolism slightly more than acarbose. Regulation of hepatic GLUT10 and intestinal GLUT12 may be important in controlling blood glucose levels.
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