The behavioral response, depamine metabolism, and characteristics of dopamine subtypes after developing the hyperlycemia were studied in the striata of rats. In animals developed hyperglycemia, the on-set duration of cataleptic behavior responded to SCH 23390 injection was delayed abd shortened, respectively. However, the cataleptic response to spiperone occurred significantly earlier in on-set and prolonged in duration. Dopamine metabolites, dihydroxyphenylacetic acid (DDPAC) and homovanillic acid (HVA), were significantly reduced in teh striata of hyeprglycemic rats. However, level of DA was significantly increased. It is noted that the ratios of DOPAC and HVA to DA were decreased, suggesting decreased tumover of DA. The affinity of striatal D-1 receptors was significantly increased without changes in the number of binding sites, while the maximum binding number of D-2 recptors was significantly increased without affecting its affinity in the diabetic rats. These results indicate that the dopaminergic activity in striatia was altered in hyperglycemic rats. Furthermore, it suggests that the upregulation of dopamine receptors might be due to the decreased dopamine matabolism.
Hyperglycemia is one of the major risk factors for stroke. Hyperglycemia can lead to a more extensive infarct volume, aggravate neuronal damage after cerebral ischemia. ${\alpha}$-Synuclein is especially abundant in neuronal tissue, where it underlies the etiopathology of several neurodegenerative diseases. This study investigated whether hyperglycemic conditions regulate the expression of ${\alpha}$-synuclein in middle cerebral artery occlusion (MCAO)-induced cerebral ischemic injury. Male Sprague-Dawley rats were treated with streptozotocin (40 mg/kg) via intraperitoneal injection to induce hyperglycemic conditions. MCAO were performed four weeks after streptozotocin injection to induce focal cerebral ischemia, and cerebral cortex tissues were obtained 24 hours after MCAO. We confirmed that MCAO induced neurological functional deficits and cerebral infarction, and these changes were more extensive in diabetic animals compared to non-diabetic animals. Moreover, we identified a decrease in ${\alpha}$-synuclein after MCAO injury. Diabetic animals showed a more serious decrease in ${\alpha}$-synuclein than non-diabetic animals. Western blot and reverse-transcription PCR analyses confirmed more extensive decreases in ${\alpha}$-synuclein expression in MCAO-injured animals with diabetic condition than these of non-diabetic animals. It is accepted that ${\alpha}$-synuclein modulates neuronal cell death and exerts a neuroprotective effect. Thus, the results of this study suggest that hyperglycemic conditions cause more serious brain damage in ischemic brain injuries by decreasing ${\alpha}$-synuclein expression.
We investigated the hypoglycemic effect of formula containing Euonymus alatus (EA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin (STZ)-induced diabetic rats. In order to iduce hyperglycemic state 25 mg/kg of STZ was injected intraperitoneally for 5 consecutive days. SD rats were randomly divided into diabetic control and treatment groups. Treatment groups were administered with either 250 mg/kg of EA and 250 mg/kg of MF (E1Ml), or 500 mg/kg of EA mixed with same dose of MF (E2M2) for 3 weeks. Blood glucose levels and body weights were measured every 5th or 6th day. E1Ml and E2M2 both significantly reduced food intake, water intake, and fasting blood and urine glucose levels as compared to those in diabetic control group in a dose dependent manner. Body weight in diabetic control group was increased slightly after 3 weeks. Treatment group, however, showed gradual increase in body weights during 3 week-period. While plasma insulin levels of the diabetic control group were decreased to the level of 387$\pm$14 pg/ml from 534$\pm$36 pg/ml, those levels in E1Ml and E2M2-treated groups were both markedly increased by 13% and 26%, respectively. Urine glucose levels in E1Ml and E2M2-treated groups were also remarkably reduced by 17 and 26% compared to the levels of diabetic control group. While expression of membrane-bound glucose transporter-4 (GLUT-4) protein in skeletal muscle was reduced by 45% in diabetic control compared to the normal control, GLUT-4 protein expressions in E1Ml and E2M2-treated groups were augmented by 2 and 3.5 times compared to the diabetic control, respectively. Pancreatic HE staining experiments showed that E2M2-treated group revealed much less infiltrated mononuclear cells, indicating that E2M2 efficiently blocked insulitis induced by multiple low dose streptozotocin. Taken together, we conclude that formula containing EA and MF may prevent or delay the development of hyperglycemia through overexpression of GLUT-4 protein in skeletal muscle and prevention of insulitis.
Kim, Yong-Hyuk;Eum, Hyun-Ae;Lee, Woo-Yong;Lee, Sang-Ho;Kim, Hyun-Young
Proceedings of the Korean Society of Applied Pharmacology
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2002.07a
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pp.219-219
/
2002
The SPP003 is a mixture of water extract from Schizandrae Fructus, Poligoni multiflori Radix, Ginseng Radix Akba and Hoelen. The aim of this study was to investigate the anti-hyperglycemic effect of SPP003 in normal and streptozotocin (STZ)-induced diabetic rats, and to monitor the toxicity of SPP003. Oral glucose tolerance test (OGTT) was performed after oral administration of SPP003 100, 300, 600 and 900 mg/kg in normal rats. Blood glucese concentration was measured at -30 min (vehicle, SPP003 or tolbutamide 60 mg/kg, 0 min (glucose treatment), 60, 120 and 180 min. Rats were administerd STZ 65mg/kg (0.1M citrate buffer, pH 4.5) intraperitoneally to induce diabetes and administered vehicle, Spp003 (100, 300 and 600 mg/kg) or tolbutamide (60 mg/kg) orally once a day for 4 weeks. Blood glucose level was measured a 0, 4, 7, 14, 21 and 29 day after initial drug administration. A single oral toxicity of SPP003 was studied in Sprague-Dawley rats of both sexes. In this study, rats were administered with doses of 1, 2 and 5 g/kg of SPP003. In glucose tolerance test, SPP003 900 mg/kg markedly decreased glucose concentration at 1 hr after glucose treatment. Blood glucose levels were much higher in STZ-diabetic rats. These increases were significantly attenuated by SPP003 600 mg/kg. SPP003 did not show any signigicant toxicity. These findings suggest that SPP003 has hypoglycemic properties in STZ-diabetic rats.
The purpose of this study was to observe the effects of the feeding physiological activity substance in Saururus chinensis Baill extract on the improvement of the blood glucose, electrolyte (Na, K, CI) concentration and lipid metabolism in the serum of streptozotocin (STZ, 55 mg/kg B.W., I.P. injection)-induced hyperglycemic rats fed the experimental diets for 5 weeks. Concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free cholesterol, cholesteryl ester ratio, triglyceride (TG) and phospholipid (PL) in serum were significantly higher in the hyperglycemic group (group NSW), STZ (I.P.)+Saururus chinensis Baill leaf 3.5 g% extract group (group NSSL) and STZ (I.P.)+Saururus chinensis Baill root 3.5 g% extract group (group NSSR) than those in the control group (group Normal, basal diet+water). But the concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free cholesterol, cholesteryl ester ratio, TG and PL in serum were remarkably lower in the groups NSSL and NSSR than those in the NSW, whereas the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration in the groups NSSL and NSSR were significantly higher than in the group NSW. Electrolyte and creatinine concentrations in serum were significantly lower in the groups NSSL and NSSR than those in the group NSW. The activities of aminotransferase (AST, ALT), creatine phosphokinase (CPK), lactate dehydrogenase (LDH) and alkaline phosphatase (ALP) in serum were remarkably lower in the groups NSSL and NSSR than in the hyperglycemic group NSW. However, no significance was found in the comperative effect of the groups NSSL and NSSR. From the above results, it was suggested that Saururus chinensis Baill was effective in the improvement of the blood glucose, electrolyte, glucide and lipid metabolism in serum of STZ-induced hyperglycemic rats.
The effect of water extract composed of panax ginseng radix rubra, acanthopanacis cortex, and cordyceps (PAC) on diabetic animal models were investigated in two different diabetic animal models. FAC water extract significantly reduced the plasma glucose levels on day 30 as compared with the diabetic control group in $KKA^Y$ obese, hyperglycemic and hyperglycemic and hyperinsulinemic mice, and also reduced the plasma glucose levels as well as total cholesterol in multiple low dose (MLD) strep tozotocin-induced diabetic SD rats. PAC water extract also showed an inhibitory effect on reduction of body weight and on development of MLD STZ-induced diabetic state. Elevated kidney hypertrophy, which is a characteristic feature shown in early stage of diabetic nephropathy and calculated as the ratio of kidney mass (g) relative to the body weight (g), was also markedly improved in PAC water extract- treated group as compared to the diabetic control group. Taken together, these data suggest that PAC water extract may have a potential as a antidiabetic agent in type 2 diabetes mellitus.
Objectives : The objective of the study was to observe the effects of different treatment lengths of Rhizoma Alismatis on diabetes mellitus. Methods : Rats were divided into three groups: normal(non-treated group), control (group administered saline for 4, 11, and 18 days), and RA (group administered 2.45mg/200g Rhizoma Alismatis for 4, 11, and 18 days). The experimental results were derived from the measurement of the levels of glucose, ALP, AST, ALT, creatinine and BUN in the serum from the rats on days 4, 11, and 18. Results : The glucose level in the serum significantly decreased on the 18th day. The ALP level in the serum did not show statistical significance. The GOT and GPT levels in the serum slightly decreased on the 4th, 11th, and 18th days, but did not show statistical significance. The creatinine level in the serum was unchanged for all of them. The BUN level in the serum did not show statistical significance. Conclusions : According to the above results, it is concluded that Rhizoma Alismatis has a therapeutic effect on diabetes mellitus with a longer period ofintake. As to influence upon the liver and kidney, there was no damage orside effects.
Background Extensive research has been conducted on islet transplantation as a possible cure for diabetes. Islet transplantation in the liver via the portal vein has shown remarkable results, but numerous other recipient sites are currently being investigated. We aimed to show the effectiveness of using a muscle flap as a recipient site for islet transplantation. Methods Islet cells were harvested from 12 isogenic Lewis rats, and then diabetes was induced in another 12 isogenic Lewis rats by streptozotocin injection. In six rats, 3,000 islets were transplanted into gastrocnemius muscle flaps, and in the other six rats, the same number of islets were transplanted into the gastrocnemius muscle. The transplanted islet cell function between the two groups was compared by means of blood glucose tests, glucose tolerance tests, immunohistochemistry, and real-time reverse transcription polymerase chain reaction. Results In the muscle flap group, blood glucose levels significantly decreased after islet transplantation. Blood glucose levels were significantly different between the two groups at 3 weeks after transplantation. The muscle flap group showed nearly normoglycemic results upon the glucose tolerance test, whereas the muscle group was hyperglycemic. Immunohistochemical evaluation showed positive results against insulin and glucagon in biopsies of both groups, and the islet cell density was higher in the muscle flap group. There were no statistically significant differences between the two groups in real-time reverse transcription polymerase chain reaction results. Conclusions Our results suggest that muscle flaps are promising candidates for islet cell transplantation.
This study has been carried out to understand the effect of SP3 and GV6 acupuncture on the hyperglycemic rat induced with Streptozotocin (STZ). Diabetes was induced in experimental groups by inraperitoneal injection of STZ (50mg/kg of body weight) twice by 24 h interval and the additional 100mg/kg 3 days after the earlier treatment. Control group was treated with tail-non acupoint, and experimental groups were treated SP3, GV6 and SP3+GV6 after hyperglycemic induction for 6 weeks. The body weight of control was lower than the experimental groups. The blood glucose was decreased significantly in the experimental groups. Glucose tolerance in acupuncture treated groups was improved. Blood cholesterol level and transaminase activites were lower in the experimental groups than in the control. In the SP3 or GV6 treated rats, hepatocyte degeneration were apparently decreased and the organelles were properly arranged. Furthermore, decrease in liver IGF-I mRNA expression was improved by the acupuncture in STZ-induced diabetic rats. In conclusion, our observation indicate that SP3 or GV6 acupoints treatment can exert beneficial effects in diabetes, with preservation of ${\beta}-cell$ function and liver function.
Kim, Hyun-Jeong;Lee, Sung-Gyu;Park, Sung-Jin;Yu, Mi-Hee;Lee, Eun-Ju;Lee, Sam-Pin;Lee, In-Seon
Korean Journal of Food Science and Technology
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v.44
no.3
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pp.367-372
/
2012
Antioxidant and anti-hyperglycemic activities of fermented red ginseng added with 5 kinds of medicinal herbs (FRGM) were investigated in vitro. Total polyphenol and total flavonoid contents in FRGM extracts were $22.41{\pm}3.51$ and $16.80{\pm}4.22{\mu}g/mg$, respectively. FRGM extracts were capable of directly scavenging DPPH free radicals ($RC_{50}=95.57{\pm}7.40{\mu}g/mL$), and then showed higher inhibitory activities for ${\alpha}$-glucosidase. This study was also conducted to evaluate the effects of FRGM extracts in streptozotocin (STZ)-induced diabetic (DM) rats. The activities with regards to serum aspartate aminotransferase and alanine aminotransferase were significantly decreased by FRGM extracts compared to those from the STZ group. The hepatic glutathione content depleted by STZ was significantly increased by FRGM extracts, but elevation of lipid peroxide content induced by STZ was significantly decreased by FRGM extracts. The decreased activities of superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase after STZ-treatment were increased through the treatment of FRGM extracts. These results indicated that fermented red ginseng added with medicinal herbs can protect against STZ-induced diabetic rats through its antioxidant properties.
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