• Journal of Pharmaceutical Investigation
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• v.33 no.2
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• pp.113-120
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• 2003

Drug interactions with food, on occasion, lead to serious nutritional and functional changes in the body as well as alternations 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 characterized by abnormal glucose homeostasis, resulting in hyperglycemia, and is associated with increased risk of micovascular, 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. The purpose of this study was to investigate thε effect of Laminaria japonica diet on the absorption, distribution, metabolism and excretion of glipizide which are frequently used in the treatment of diabetes. Diabetic rats induced by streptozotocin were employed in this study. Blood concentrations of oral hypoglycemic agents 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 glipizide in normal rats treated with Laminaria japonica diet showed significant increase in AUC, $k_{a},\;t_{1/2},\;t_{max}$ and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption. Administration of glipizide in diabetic rats treated with Laminaria japonica diet showed significant increase in $t_{1/2}\;and\;t_{max}$, and decrease in $C_{max}$, compared to those without Laminaria japonica diet. This might also result from adsorption of glipizide on components of Laminaria japonica, causing delayed absorption and flattened blood concentration of glipizide. 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 glipizide caused by long-term Laminaria japonica diet.

• Nutrition Research and Practice
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• v.8 no.4
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• pp.404-409
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• 2014

BACKGROUND/OBJECTIVES: The number of diabetic patients has recently shown a rapid increase, and delayed wound healing is a major clinical complication in diabetes. In this study, the wound healing effect of Hominis placenta (HP) treatment was investigated in normal and streptozotocin-induced diabetic mice. MATERIALS/METHODS: Four full thickness wounds were created using a 4 mm biopsy punch on the dorsum. HP was injected subcutaneously at the middle region of the upper and lower wounds. Wounds were digitally photographed and wound size was measured every other day until the 14th day. Wound closure rate was analyzed using CANVAS 7SE software. Wound tissues were collected on days 2, 6, and 14 after wounding for H/E, immunohistochemistry for FGF2, and Masson's trichrome staining for collagen study. RESULTS: Significantly faster wound closure rates were observed in the HP treated group than in normal and diabetes control mice on days 6 and 8. Treatment with HP resulted in reduced localization of inflammatory cells in wounded skin at day 6 in normal mice and at day 14 in diabetic mice (P < 0.01). Expression of fibroblast growth factor (FGF) 2 showed a significant increase in the HP treated group on day 14 in both normal (P < 0.01) and diabetic mice (P < 0.05). In addition, HP treated groups showed a thicker collagen layer than no treatment groups, which was remarkable on the last day, day 14, in both normal and diabetic mice. CONCLUSIONS: Taken together, HP treatment has a beneficial effect on acceleration of cutaneous wound healing via regulation of the entire wound healing process, including inflammation, proliferation, and remodeling.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.184-188
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• 2007

The major goal in the treatment of diabetes mellitus is to achieve near-normal glycemic control. To optimize both fasting blood glucose and postprandial glucose levels is important in keeping blood glucose levels as close to normal as possible. ${\alpha}-Glucosidase$ is the enzyme that digests dietary carbohydrate, and inhibition of this enzyme could suppress postprandial hyperglycemia. The purpose of this study was to test the inhibitory activity of methanol extract of Euonymus alatus on ${\alpha}-glucosidase$ in vitro and in vivo to evaluate its possible use as an anti-diabetic agent. Yeast ${\alpha}-glucosidase$ inhibitory activities of methanol extract of E. alatus were measured at concentrations of 0.50, 0.25, 0.10, and 0.05 mg/ml. The ability of E. alatus to lower postprandial glucose was studied in streptozotocin-induced diabetic rats. A starch solution (1 g/kg) with and without E. alatus extract (500 mg/kg) was administered to diabetic rats by gastric intubation after an overnight fast. Plasma glucose levels were measured at 30, 60, 90, 120, 180, and 240 min. Plasma glucose levels were expressed in increments from baseline, and incremental areas under the response curve were calculated. Extract of E. alatus, which had an $IC_{50}$ value of 0.272 mg/ml, inhibited yeast ${\alpha}-glucosidase$ activity in a concentration-dependent manner. A single oral dose of E. alatus extract significantly inhibited increases in blood glucose levels at 60 and 90 min (p<0.05) and significantly decreased incremental response areas under the glycemic response curve (p<0.05). These results suggest that E. alatus has an antihyperglycemic effect by inhibiting ${\alpha}-glucosidase$ activity in this animal model of diabetes mellitus.

• Proceedings of the Korean Biophysical Society Conference
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• 1999.06a
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• pp.61-62
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• 1999

;The mechanisms inducing hypertension are actively investigated and are still challenging topics. Basically hypertension must be caused by the disorder of $Ca^{2+}$ metabolism in vascular smooth muscle, such as the increase of $Ca^{2+}$ influx, the decrease of ci+ efflux, or the change of sensitivity of contractile protein etc. The one of cause of the increase of ci+ influx may be the change of ci+ channel activity. Even though the relationships of ci+ channel activity and hypertension were studied using various hypertension models, still it is not clear how much change of $Ca^{2+}$ channel activity in diabetes mellitus (DM) induced hypertension is occurred. We induced DM hypertension in SD rat and compared the $Ca^{2+}$ channel activity with age-matched normotensive SD rat. For inducing DM hypertension, left kidney was removed with 200 gm rat and, after 1 month, 60 mg/kg of streptozotocin was injected into peritoneal space to induce diabetes mellitus. Usually after 4-6 weeks, hypertension was fully induced. For isolating vascular smooth muscle cells (VSMC), we used mesenteric arteriole (3rd - 4th branch of mesenteric artery) of which diameter is below 150 urn. VSMCs were isolated enzymatically. $Ca^{2+}$ current was measured using whole cell patch clamp technique. All experiments were performed at $37^{\circ}C$. The cell membrane area of VSMC of DM hypertensive rat is larger than that of control VSMC($36.6{\pm}3.64{\;}pF{\;}vs{\;}22.4{\pm}1.29{\;}pF, {\;}mean{\pm}S.E.$) When we compared the current amplitude, the $Ca^{2+}$ current amplitude in VSMC of DM hypertensive rat is much larger than that in VSMC of normotensive age-matched rat. After $Ca^{2+}$ current amplitude was normalized by cell membrane area, the current amplitude in DM hypertension is increased to $249.1{\pm}15.9{\;}%{\;}(mean{\pm}S.E.M)$, which means the ;absolute current amplitude is about 4 times larger in DM hypertension. When we compared the steady state activation and inactivation. there were no noticeable differences. From these results. one of cause of the DM hypertension is due to the increase of $Ca^{2+}$ current amplitude. But it need further study why the $Ca^{2+}$ current is so large in VSMC of DM hypertension and how much $Ca^{2+}$ influx through $Ca^{2+}$ channel contribute to the increase of intracellular $Ca^{2+}$ and eventually contribute to development of hypertension.ypertension.

• Journal of Life Science
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• v.17 no.11
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• pp.1571-1575
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• 2007

This research was carried out to investigate the effects of Hambag mushroom on the oxidative stress in diabetic rats, Sprague-Dawley. The diabetic rats induced by streptozotocin were fed with hambag mushroom-powder(G. frondosa) for 6 weeks. For the level of oxidative stress in liver and pancreas tissues, it was studied by measuring LPO (lipid oxide) level as an indicator of lipid peroxidation, XOD(xanthine oxidase) as one of important sources for free radicals and the levels of GSH and GST as anti-oxidant systems. Also, as an indicator of liver damaged by oxidative stress, the activities of serum ALT and AST were measured. It was observed that the levels of ALT, AST, LPO and XOD were higher by about two times in both tissues from diabetic rats than in those from control rats. This indicates that the oxidative stress induced by diabetes caused the tissues damages. However, these levels were decreased in the tissues from rats with hambag mushroom-powder. Futhermore, the activity of GST were higher in both tissues from diabetic rats fed with hambag mushroom-powder than in those from diabetic rats. Thus, it is considered that the hambag mushroom-powder decreases the level of oxidative stress by increasing activity of anti-oxidant system such as GSH and GST. It is suggested that the hambag mushroom-powder can be useful for preventing the tissues damaged by diabetes-induced oxidative stress.

• Korean journal of food and cookery science
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• v.13 no.4
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• pp.500-506
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• 1997

The purpose of this study was to investigate the effect of H$_2$O fraction of Dioscorea japonica Thunb (DJT) with vitamin E on blood glucose and fat metabolism in streptozotocin (STZ) diabetic rats. Sprague-Dawley rats (200∼230 g) weighing were divided into five groups; the normal group, the STZ-control group, the DJT group, the DJT-vitamin E group and the vitamin E group. Diabetes was induced in the male rats by injection of STZ into tail vein at a dose of 45 mg/kg body weight. The H$_2$O fraction of DR (500 mg/kg) and 10 mg/kg of vitamin E (㎗-${\alpha}$-tocopherol) given orally were administered for 14 days. The body weight was monitored and levels of hematocrit, protein and glucose were determined. The plasma concentrations of cholesterol; triglyceride, free fatty acid and HDL-cholesterol were measured. The activities of aminotranseferase were analysed. The body weight gain was shown no significantly higher in the normal group than all STZ groups. The administration of H$_2$O fraction of DJT and vitamin E showed a significant increase in plasma protein concentrations. The all STZ group was formed to be effective in decreasing blood glucose levels. Plasma insulin concentrations were highered in diabetic rats fed on H$_2$O fraction of DJT. Plasma triglyceride and free fatty acid levels were lower in the vitamin E group than the STZ-control group. The plasma cholesterol levels of all STZ groups were not significantly different and HDL-cholesterol levels were increased in all STZ groups fed on H$_2$O fraction of DJT and vitamin E, specially in the DJT-vit. E group. The all STZ group does not significantly change aminotransferase activity of diabetic rats. These results indicated that DJT was a potential candidate for a treatment of diabetes which can enhance insulin activity The effect of vitamin E on insulin activity will be examined in more detail.

• The Korean Journal of Pharmacology
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• v.24 no.2
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• pp.221-232
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• 1988

Studies were conducted to determine whether reduced renal blood flow (RBF) exhibited by rats with uncontrolled, streptozotocin (STZ)-induced diabetes is attributable to diabetes-associated, enhanced renal vasoconstrictor influence of endogenous thromboxane $(TX)A_2$. Rats which were injected with STZ after pretreatment with 3-O-methyl glucose (3OMG), an agent which prevents STZ-induced hyperglycemia, were also studied. Basal values of total RBF (RBF; ml $min^{-1}$ $gKw^{-1}$; electromagnetic flow probe), systemic arterial pressure (BP; mm Hg) and renal vascular resistance (RVR;BP $RBF^{-1})$in pentobarbital-anesthetized rats during a control period were $5.9{\pm}0.3$(P<0.1_{VS}. CR), $115{\pm}3$ and $20.3{\pm}1.0$(P<0.1_{VS}. CR) for STZR (n=15), and $8.4{\pm}0.4$, $123{\pm}3$ and $15.1{\pm}0.8$ for age-matched control rats (CR; n= 15), respectively. Basal values of RBF, BP and RVR in 3OMG pretreated STZR were identical to CR. In preparations shown capable of renal vasodilatation, OKY 1581 (1 mg/kg, i.v. followed by 0.4 mg/kg min infusion) abolished arachidonate-induced $(TX)A_2$ synthesis, but did not alter basal BP, RBF or RVR in either STZR or CR (n=4/group). Similarly, i.r.a. infusion of SQ29548 (100 ng/ml RBF) abolished renal vasoconstriction induced by a TX/prostaglandin endoperoxide mimic, U46619, but had no discern able affect on RVR in either STZR (n=8) or CR (n=8). The data indicates that $TXA_2$ does not participate in the elevated basal RVR of STZR which are associated with the diabetic state.

• Journal of Nutrition and Health
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• v.31 no.9
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• pp.1377-1384
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• 1998

The purpose of this study was to investigate the effect of H$_2$O fraction of Dioscorea japonica Thunb(DJT) with selenium(Se) treatment on blood glucose and lipid metabolism in streptozotocin(STZ)-induced diabetic rats. Male Sprague-Dawley rats(180-220g) weighing were divided into five groups, that is one normal group and four diabetic experimental groups : the STZ-control group, the DJT group, the DJT-Se group and the Se group. Diabetes mellitus was induced in the male rats by injection of STZ into the tail vein at a dose of 45mg/kg B.W. The H,0 fraction of DJT(500mg/kg) given orally were administered for 14 days. The Se treated group were fed a AIN-76 recommendation diet mixed with Na$_2$SeO$_3$(2mg/kg diet), which was prepared fresh daily. The body weight and food intake was monitored daily and plasma levels of glucose, insulin, hematocrit and protein were determined. The plasma concentrations of cholesterol, HDL-cholesterol, triglyceride and fire fatty acid were measured. The activities of aminotrans ferase were analysed. The body weight gain was shown to be significantly higher in the normal group than all diabetic groups. The blood glucose levels of the DIT-Se group was significantly lower compared to those of the experimental groups. The administration of H$_2$O fraction of DJT and selenium showed an increase in plasma protein concentrations. The plasma cholesterol levels of all STZ-groups were not significantly different and HDL-cholesterol levels were increased in the diabetic experimental groups fed on H$_2$O fraction of DJT or Se supplementation. Plasma triglyceride levels were lower in the DJT-Se and Se group than in the STZ-control group. free fatty acid levels were not significantly differ among STZ-control groups. STZ treatment increased aminotransferase activity and that of DJT group was highest. In conclusion, the data from the present experiments indicate that the treatment of the H$_2$O fraction of DJT with selenium showed a synergistic effect and the two can have an influence on hyperg1ycemia and lipid metabolites when administered together. (Korean J Nutrition 31(9) : 1377-1384, 1998)

• Journal of the Korean Society of Food Science and Nutrition
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• v.24 no.2
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• pp.183-194
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• 1995

The purpose of this study was to investigate the effect of vitamin E on the synthesis of the metallothionein in the liver of streptozotocin (STZ)-induced diabetic rats. Sprague-Dawley male rats($220{\pm}10mg$) were randomly assigned to one control and three STZ-diabetic groups. Diabetic groups were classified to STZ-0E(vitamine E free diet), STZ-40E(40mg vitamin E/kg of diet) and STZ-400E(400mg vitamin E/kg of diet) according to the level of vitamin E supplementation. Blood glucose levels of STZ-diabetic rats were three times higher than that of control. The contents of vitamin E in liver were lower signifciantly STZ-0E, STZ-40E groups by 50%, 36% compared with that of control. Lipid peroxide values(LPO) in liver were higher 5.6 and 2.5 times in STZ-0E and STZ-40E groups than that of control. Plasma cortisol levels were higher STZ-0E and STZ-40E groups compared with those of control, but cortisol levels were lower significantly in STZ-400E group compared with those of the STZ-0E and the STZ-40E groups. The plasma insulin levels were lower in all three STZ-diabetic group compared with that of control, but were not affected by the level of dietary vitamin E. The metallothionein (MT) contents in liver, kidney and small intestine were five times higher in STZ-0E, STZ-40E and STZ-400E compared with that of control, but STZ-400E group was lower in the MT contents in tissues compared with that of STZ-40E group. Zn-MT peak in STZ-diabetic rats liver increased than that of control by Sephadex G-75, and Zn-MT peak divided into MTI and MTII peaks by DEAE Sephadex A-25 column chromatography. The present results indicate that STZ-induced diabetic rats are more sensitive to oxidative stress, leading to the acceleration of lipid peroxidation process, which can be more promoted low level of dietary vitamin E. And the result may that increase synthesis of MT induced in the liver of diabetic rats increased so it can be sure that the diabetes is one of the MT induce factor by free radical generation. And high vitamin E supplementation reduced total MT contents of liver, kidney and small intestine and the peak of purified Zn-MT. Through the results of these experiments, we can conclude that MT might be the free radical scavenger.

• Journal of Nutrition and Health
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• v.39 no.6
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• pp.513-519
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• 2006

The effects of fractions of ethanol extract of Benincasa hispida (wax gourd) on lipid levels and lipid peroxidation in streptozotocin (STZ) induced diabetic rats were examined. Sprague-Dawley rats were induced diabetes mellitus by STZ injection (45 mg/kg) into the tail vein and were divided into 5 groups: normal, STZ-control, three experimental diabetic groups [chloroform $(CHCl_3)$ fraction group, butanol (BuOH) fraction group, and water fraction group]. Fractions of ethanol extract of Benincasa hispida were administered orally into the diabetic rats for 14 days. The liver glycogen levels of $CHCl_3$ fraction group and the muscle glycogen levels of BuOH and water fraction groups were significantly higher than that of STZ-control group. Pancreas protein levels of BuOH and water fraction groups were significantly higher than that of STZ-control group. The liver cholesterol level of BuOH and water fraction groups were significantly lower when compared with the STZ-control group. The level of liver triglyceride in BuOH and water fraction groups were significantly higher than that of STZ-control group. Malondialdehyde (MDA) levels in liver of normal and diabetic groups were not significantly different. In the pancreas, the MDA levels of BuOH and water fraction group were significantly lower than that of STZ-control group. The results suggested that the supplementation of the BuOH and water fractions of Benincasa hispida extract could be beneficial for the diabetic complications and damages from the lipid peroxidation.