• The Korean Journal of Food And Nutrition
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• v.21 no.3
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• pp.328-335
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• 2008

The principal objective of this study was to assess the effects of chitosan oligosaccharide supplementation on the improvement of blood glucose, lipid components and enzyme activities in the serum of streptozotocin(STZ, 55 mg/kg B.W., I.P. injection)-induced hyperglycemic rats fed on experimental diets for 5 weeks. The concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, free cholesterol, cholesteryl ester ratio, triglycerides(TG) and phospholipids(PL) in serum were remarkably higher in the hyperglycemic group(group BSW) and STZ(I.P.)+chitosan oligosaccharide supplementation group(group ECW) than those in the control group(group BW, basal diet+water). However the concentrations of blood glucose, total cholesterol, atherosclerotic index, LDL, LDL-cholesterol, tree cholesterol, cholesteryl ester ratio, TG and PL in serum were lower in the ECW group than in the BSW group, whereas the ratio of HDL-cholesterol concentration to total cholesterol and HDL-cholesterol concentration in the ECW group were higher than in the BSW group. The activities of alkaline phosphatase(ALP) and aminotransferase(AST, ALT) in serum were lower in the ECW group than in the hyperglycemic BSW group. The results shown above suggested that chitosan oligosaccharide supplementation effectively improves blood glucose, lipid composition and enzyme activities in the sera of STZ-induced hyperglycemic rats.

• Environmental Analysis Health and Toxicology
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• v.19 no.3
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• pp.287-294
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• 2004

Diabetic complication is one of major risk factors leading to vascular disease such as atherosclerosis, stroke, coronary heart disease and etc. Several factors affecting the acceleration of diabetic vascular complication have been known such as hypertension, hyperlipidemia, immune complex and genetic factors. To screen and develop new therapeutics agents for diabetic vascular complication, it is strongly needed to develop animal models for diabetic complications. However in rodents models, diabetic complications is not well developed. Furthermore to assess the possibility of new therapeutics for diabetic vascular complications, diabetic animal models which have the risk factors of diabetic complications is needed. We aim to develop and establish an diabetic animal model which have diabetic complications with hyperlipidemia which is one of risk factors for diabetic complications. We induced insulin -dependent diabetes by intra. venous injection of streptozotocin (35 mg/kg/day) in RICO rats which is a spontaneous animal model for hyperlipidemia. Our models (STZ RICO) showed hyperglycemia, persistent high level of plasma cholesterol and triglyceridemia with severe diabetic renal changes until 28 weeks after induction of diabetes. STZ-RICO rats could be used for the evaluations of newly developed diabetic drugs.

• YAKHAK HOEJI
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• v.46 no.6
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• pp.411-415
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• 2002

We compared the hypoglycemic effects of Ginseng Radix Alba (GRA) and Mori Folium (MF) in multiple low dose (MLD) streptozotocin(STZ)-induced diabetic rats. In order to induce 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 500 mg/kg of GRA (G500), 500 mg/kg of MF (M500), or 250 mg/kg of GRA mixed with same dose of MF (GM250) for 3 weeks. Blood glucose level and body weight were measured every 5th day. G500 and M500 both significantly reduced blood glucose levels as compared to the diabetic control group (diabetic control, 458.3$\pm$25.4 mg/dl; G500, 275.0$\pm$12.0; M500, 278.0$\pm$15.4; GM250, 324.0$\pm$18.4). While body weight in diabetic control group was decreased slightly after 3 weeks, treatment groups showed gradual increases of body weight during 3 week-period. Plasma insulin level was increased by treatment with GRA, but those levels in M500 and GM250 groups were similar to the diabetic control (normal control, 32.0$\pm$13.9 $\mu$IU/mι; diabetic control, 12.4$\pm$1.9; G500, 17.5$\pm$3.4; M500, 11.1$\pm$3.2; GM250, 10.5$\pm$t3.7). Urine glucose levels were also remarkably reduced in all treatment groups (normal control, 0.0$\pm$0.0 g/day; diabetic control, 11.4$\pm$2.5; G500, 4.9$\pm$0.2; M500, 5.7$\pm$1.6 ; GM250, 8.2$\pm$0.2). At the second and third week of the treatment, food and water intakes were determined. At the third week, food and water intakes were significantly decreased in all treatment groups. Taken together, we may conclude that GRA and MF alone may prevent or delay the development of hyperglycemia, however, synergistic hypoglycemic activity was not be seen in group treated with mixed formula of GRA and MF when compared to GRA or MF alone.

• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.95-102
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• 1995

The pathogenesis of diabetic nephropathy is still not completely understood while renal disease is one of the most common disabling complications of diabetes. We, in the present study, investigated the possible involvement of oxidative stress in the development of diabetic nephropathy. To hasten the development of diabetic nephropathy, streptozotocin was injected to unilaterally nephrectomized rats (NEPH-STZ). Eight weeks later, NEPH-STZ rats developed severe hyperglycemia, proteinuria, and hypertension. The kidneys of these rats showed compensatory hypertrophy and mesangial expansion. In contrast, the rats with streptozotocin injection alone (STZ) did not increase urinary protein excretion. Nephrectomized non-diabetic rats (NEPH) developed increased urine protein excretion, but without prominent renal morphological changes. However, oxidation of renal cortical tissue protein significantly increased in all 3 groups of NEPH, STZ and NEPH-STZ in comparison to control rats (CONT). The result indicates the non-specificity of the oxidative tissue damage and suggests that the oxidative damage is hardly a sole mechanism leading to the development of the diabetic nephropathy. However, it would still be a contributing factor considering that the oxidative stress is a common final pathway mediating tissue damages in chronic diabetic complications and other serious illness.

• Journal of the Korean Society of Food Science and Nutrition
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• v.32 no.6
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• pp.921-925
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• 2003

To control blood glucose level as close to normal is the major goal of treatment of diabetes mellitus. $\alpha$-glucosidase is the enzyme to digest dietary carbohydrate and inhibition of $\alpha$-glucosidase could suppress postprandial hyperglycemia. The methanol extract of soybean sprout was tested for the inhibitory activities against $\alpha$-glucosidase in vitro. Soybean sprout extract inhibited yeast $\alpha$-glucosidase activity by 24.5% at the concentration of 5 mg/mL. The methanol extract of soybean sprout was subsequently subjected to sequential fractionation with hexane, ethyl acetate, butanol and water. Among the fractions tested ethyl acetate-soluble fraction showed relatively strong inhibition against $\alpha$-glucosidase by 36.3% at the concentration of 5 mg/mL. Acarbose, standard $\alpha$-glucosidase inhibitor, inhibited $\alpha$-glucosidase activity by 40.1%. The ability of soybean sprout extract to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. Starch solution (1 g/kg) with and without the methanol extract of soybean sprout (500 mg/kg) was administered to diabetic rats after an overnight-fast by gastric intubation. A single oral dose of soybean sprout extract inhibited the increase in blood glucose levels significantly at 60, 90, 120, 180 min (p<0.05) and decreased incremental response areas under the glycemic response curve significantly (p<0.05). These results suggest that soybean sprout might exert hypoglycemic effect by inhibiting $\alpha$-glucosidase activity.

• Journal of Ginseng Research
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• v.27 no.2
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• pp.56-61
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• 2003

This study was designed to compare the antidiabetic activities between Ginseng Radix Alba (GRA), Ginseng Radix Rubra (GRR) and Panax Quinquefoli Radix (PQR) in multiple low dose (MLD) streptozotocin (STZ) (20 mg/kg i.p injection far 5 days) induced diabetic rats. In the glucose tolerance test, 500 mg/kg of each ginseng ethanol extract was administered intraperitoneally 30 min before glucose challenge. While GRA failed to lower blood glucose level, GRR and PQR both significantly prevented the hyperglycemia when compared with the control group. In the MLD STZ-induced diabetic rats, 300 mg/kg of each ginseng ethanol extract was administered intraperitoneally for 2 weeks. Plasma glucose and insulin levels were markedly improved in all treatment groups. While GRR showed the highest antidiabetic activity, and GRA and PQR revealed somewhat equipotent antidiabetic activities, but less than that in GRR-treated group as far as blood parameters and diabetic symptoms such as polyphagia and polydipsia are concerned. Blood glucose levels were closely associated with plasma insulin levels, and this result may suggest that ginseng ethanol extracts showed the activity to enhance insulin secretion as well as preventing destruction of pancreatic islet cells. To elucidate the relationship between antidiabetic activity and ginsenoside profiles, seven major ginsenosides were quantified by HPLC. We figured out the fact that protopanaxatriol (PPT): proptopanaxadiol (PPD) ratio might play an important role in its hypoglycemia effects.

• Journal of the Korean Society of Food Science and Nutrition
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• v.34 no.6
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• pp.825-832
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• 2005

This study was conducted to investigate the effect of extract of Fomes fomentarius (FF) on blood glucose, lipid profile, antioxidant enzymes and immune cells in streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats were divided into control, STZ-induced diabetic group (DM), STZ plus FF water extract treated group (DM-FW 200) and STZ plus FF methanol extract treated group (DM-FM 200). FW (200 mg/kg BW) and FM (200 mg/kg BW) were orally administered once a day for 14 days. Admdinistering FW and FM to STZ-induced diabetic rats lowered the blood glucose level. The supplementation of FW and FM suppressed the increase in the total cholesterol and triglyceride levels in the serum and liver of the diabetic rats. The high density lipoprotein-cholesterol level and glutathione peroxidase activity were higher in the FF-sup-plemented group compared to the diabetic group. Administering FW and FM increased the suppress in the serum complement component C3, whole blood B-cell, T-cell, helper T cell and suppressor T cell of the diabetic rats. Therefore, it could be suggested that FW and FM are alleviated the diabetic complication through enhancing the hyperglycemia and preventing diabetic complications.

• Journal of the Korean Society of Food Science and Nutrition
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• v.37 no.12
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• pp.1554-1559
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• 2008

This study was performed to investigate the hypoglycemic effect of single and repeated oral administration of medicinal herbal mixture (AD) in streptozotocin (STZ) induced diabetic rats. Angelica decursiva, Lycium chinense and Adenophora triphylla var. japonica Hara were selected by oral glucose tolerance test (OGTT) and mixed for AD mixture. In an oral glucose tolerance test, the AD inhibited the increase in blood glucose levels at 1 hr and 2 hr and decreased incremental glycemic response area under the curve. In a single administration of AD1 (100 mg/kg) and AD2 (500 mg/kg), significant reductions by 5.3% and 12.3% were observed in fasting blood glucose level for 4 hours. During the 1 month of the experimental period, AD1 and AD2 was given to the STZ induced diabetic rats. At 4th week, the fasting blood glucose levels of AD1 and AD2 caused a fall of 25.5% and 37.9%, respectively. In addition, the body weights were decreased by 7.7% (AD1) and 1.7% (AD2), respectively, compared with diabetic control (DC, decreasing of 10.2%). This study suggests that AD could be potentially useful for fasting and post-prandial hyperglycemia treatment and all these effects concluded to the use of this plant extract to manage diabetes mellitus.

• Korean Journal of Environmental Biology
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• v.24 no.2 s.62
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• pp.102-111
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• 2006

The increased occurrence of hyperglycemia and oxidative stress in streptozotocin (STZ) induced type I diabetes has been implicated in the etiology and pathology of disease complication. STZ has known to be genotoxic in a variety of assays including tests for microbial mutagenesis and unscheduled DNA synthesis in rat kidney. Diabetes mellitus (DM) is a pathologic condition, resulting in severe metabolic imbalances and non-physiologic changes in many tissues. We examined the effect of gamma radiation and KWNP on preventing the development of insulin dependent diabetes mellitus using streptozotocin-induced Fisher 344 diabetic rats. The hematological values (red blood cell and white blood cell), serum biochemical constituents-alkaline phosphatase (ALP), total cholesterol, triglycerides and insulin-were checked and the organs (testis, spleen and kidney) were weighed. The gonad indices of the STZ treated groups were much lower than the value of the control group. But the gonad indices of the KWNP treated groups were higher than those of the treated groups. The ratio of the weight of kidney to the body weight of the STZ treated groups was higher than that of the control group. The value of the diabetic group treated with KWNP after irradiation (F group) was lower than the other STZ treated groups. The white blood cell and ALP values of the F group were lower than the other STZ groups, as well. The cholesterol and triglyceride values of all the KWNP treated groups were significantly lower than the other groups. A significant increase (about 10 times) of insulin was detected in the F group. The results of hematological assay showed the distinctive damage in the irradiated and STZ treated groups. The quantity of apoptotic cells in seminiferous tubule of testis confirmed a serious damage as assessed in the STZ treated groups. These experimental results have revealed that treatment of the products of KWNP after irradiation has the antidiabetic effect in the STZ-induced diabetic rats. But the F group showed higher recuperative power. These experimental results have revealed that treatment of the gamma irradiation and KWNP have the recovering effect in the STZ-induced diabetic rats.

• Journal of Pharmaceutical Investigation
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• v.33 no.3
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• pp.171-178
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alterations of pharmacological effect. It, therefore, should be necessary to take drug interactions with food into consideration for effective and safe therapeutics. Diabetes mellitus is a heterogeneous group of disorders characterzed by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of microvascular, macrovascular, and neuropathic complications. However, the precise mechanism of diabetes mellitus remains unclear. Three basic objectives in the care of diabetic patients are maintaining optimal nutrition, avoiding hypo- or hyperglycemia and preventing complications. Laminaria japonica is a brown macroalgae which can be used as a functional diet due to high content of diatery fiber. The purpose of this study was to investigate the effect of Laminaria japonica diet on the pharmacokinetics of metformin which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agent, metformin, were measured by HPLC and resultant pharmacokinetic parameters were calculated by RSTRIP. The mechanisms of drug interaction with food were evaluated on the basis of pharmacokinetic parameters such as $k_{a},\;t_{1/2},\;C_{max},\;t_{max}$, and AUC. Administration of metformin in normal and diabetic rats treated with Laminaria japonica diet showed significant decrease in AUC, $C_{max},\;and\;k_a$, and increase in $t_{max}$, compared to those with normal diet. This might result from adsortion of metformin on components of Laminaria japonica, causing delayed absorption. The oral glucose test showed that Laminaria japonica diet could lower blood glucose level probably through either inhibiting the activity of disaccharidases, intestinal digestive enzymes, or delaying the absorption of glucose. More studies should be followed to fully understand pharmacokinetic changes of metformin caused by long-term Laminaria japonica diet.