Proceedings of the Korean Society of Applied Pharmacology
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2008.04a
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pp.5-20
/
2008
GLP-1-based drugs (GLP-1 analogues and DPP IV inhibitors) and incretin mimetics are currently one of the most exciting classes of agents for type II diabetes. GLP-1, a gut peptide, is an incretin that potentiates glucose-dependent insulin release from the pancreas, slows GI-transit and stimulates the proliferation of beta-cells. DPP IV inhibitors act like incretins by inhibiting DPP IV which inactivates GLP-1. LC15-0133 is a competitive, reversible DPP IV inhibitor ($IC_{50}$ = 24 nM, Ki=0.247 nM) with excellent selectivity over other critical human proteases such as DPP II, DPP 8, elastase, trypsin. and urokinase. LC15-0133 showed long half-life and good bioavailability in rats and dogs. Inhibition of plasma DPP IV activity by LC15-0133 was kept more than 50% 24 hours after oral dosing in rats and dogs at 0.1 mg/kg and 0.02 mg/kg, respectively. The Minimum effective doses of LC15-0133 were 0.01 mg/kg for lowering blood glucose excursion during oral glucose tolerance test and 0.1 mg/kg for increasing glucose-induced GLP-1 response in C57BL/6 mice. Repeat oral administration of LC15-0133 for 1 month delayed the progression to diabetes and reduced HbA1c levels in a dose-dependent manner in Zucker Diabetic Fatty rats. In conclusion, LC15-0133 is a novel, potent, selective and orally active DPP IV inhibitor and showed an excellent blood glucose lowering effects in various animal models.
Aloe vera gel supercritical $CO_2$ extract (AVGE) has been shown to contain five phytosterols, reduce visceral fat accumulation, and influence the metabolism of glucose and lipids in animal model experiments. Recent epidemiologic studies have shown that obesity is an established risk factor for several cancers including colorectal cancer. Therefore, we examined the effects of AVGE on intestinal polyp formation in Apc-deficient Min mice fed a high-fat diet. Male Min mice were divided into normal diet (ND), high fat diet (HFD), low dose AVGE (HFD+LAVGE) and high dose AVGE (HFD+HAVGE) groups. The ND group received AIN-93G diet and the latter 3 groups were given modified high-fat AIN-93G diet (HFD) for 7 weeks. AVGE was suspended in 0.5% carboxymethyl cellulose (CMC) and administered orally to mice in HFD+LAVGE and HFD+HAVGE groups every day (except on Sunday) for 7 weeks at a dose of 3.75 and 12.5 mg/kg body weight, respectively. ND and HFD groups received 0.5% CMC alone. Between weeks 4 and 7, body weights in the HFD and HFD+LAVGE groups were reduced more than those in the ND group. However, body weights were not reduced in the HFD+HAVGE group. Mice were sacrificed at the end of the experiment and their intestines were scored for polyps. No significant differences were observed in either the incidence and multiplicity of intestinal polyps (${\geq}0.5$ mm in a diameter) among the three groups fed HFD. However, when intestinal polyps were categorized by their size into 0.5-1.4, 1.5-2.4, or ${\geq}2.5$ mm, the incidence and multiplicity of large polyps (${\geq}2.5$ mm) in the intestine in the HFD+HAVGE group were significantly lower than those in the HFD group. We measured plasma lipid (triglycerides and total cholesterol) and adipocytokine [interleukin-6 and high molecular weight (HMW) adiponectin] levels as possible indicators of mechanisms of inhibition. The results showed that HMW adiponectin levels in the HFD group were significantly lower than those in the ND group. However, the levels in the HFD+HAVGE group were significantly higher than those in the HFD group. These results indicate that HAVGE reduced large-sized intestinal polyps and ameliorated reduction in plasma HMW adiponectin levels in Min mice fed HFD.
Journal of the Korean Society of Food Science and Nutrition
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v.28
no.3
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pp.654-662
/
1999
The purpose of this study was to investigate the effects of vitamin E on the antioxidative defense system of kidney in streptozotocin induced diabetic rats. Sprague Dawley male rats weighing 100$\pm$10g were randomly assigned to one normal and three STZ induced diabetic groups, which were subdivided into vitamin E free diet(DM 0E group), 40mg vitamin E per kg diet(DM 40E group) and 400mg vitamin E per kg diet(DM 400E group). Vitamin E level of normal group was 40 mg per kg diet. Diabetes was experimentally induced by intravenous injection of 55mg/kg of body weight of streptozotocin(STZ) in citrate buffer(pH 4.3) after 4 weeks feeding of experimental diets. Animals were sacrificed at the 6th day of diabetic states. There were no significant on body weights, food intakes, and food efficiency ratio before the diabetic occurrence. But after the injection of STZ, body weights and food efficiency ratios were significantly decreased and the food intakes was increased. Kidney weights were significantly increased in diabetic groups compared to normal group. However, there were no significant differences among the diabetic groups. Plasma insulin levels of diabetic groups were significantly decreased, whereas, blood sugar levels were increased compared to that of normal group. There were no significant differences among diabetic groups in plasma insulin and glucose levels. Activities of superoxide dismutase(SOD) in DM 0E and DM 40E groups were signi ficantly decreased by 33% and 27%, respectively, compared to normal group. But that of DM 400E group was increased by 35% compared to DM 0E group. Activity of glutathione peroxidase(GSHpx) in DM 0E group was decreased by 20% compared with normal group. GSHpx activity in DM 400E group was increased by 29% compared to normal group. The contents of vitamin E in kidney were 58% and 49% lower in DM 0E and DM 40E group, respectively, than normal group. There was no significant difference in renal vitamin E contents between DM-400E group and normal group. The contents of superoxide radical(O2 ) in kidney were 150% and 98%, respectively, higher in DM 0E and DM 40E groups than normalgroup. DM 400E and normal groups were similar levels in their superoxide radical contents of kidneys. These results indicate that vitamin E functioned as chain breaking antioxidant in kidney such as in other tissues.
Requirements of dietary chloride (dCl) and chloride salts were determined by using $4{\times}2$ factorial arrangement under four phase feeding program. Four levels (0.31, 0.45, 0.59 and 0.73%) and two sources ($NH_4Cl$ and $CaCl_2$) of the dCl were allocated to 1,472 chicks in eight dietary treatments in which each treatment was replicated four times with 46 birds per replicate. The four phase feeding program was comprised of four dietary phases: Prestarter (d 1 to 10), Starter (d 11 to 20), Grower (d 21 to 33) and Finisher (d 34 to 42); and diets were separately prepared for each phase. The cations, anions, pH, dissolved oxygen (DO), temperature, electrical conductivity (EC), total dissolved solids (TDS) and salinity were analyzed in drinking water and were not affected by dietary treatments. BW gain (BWG; $p{\leq}0.009$) and feed:gain (FG; $p{\leq}0.03$) were improved in $CaCl_2$ supplemented diets during d 1 to 10. The maximum response of BWG and FG was observed at 0.38% and 0.42% dCl, respectively, for d 34 to 42. However, the level of dCl for BWG during d 21 to 33 ($p{\leq}0.04$) and d 34 to 42 ($p{\leq}0.009$) was optimized at 0.60% and 0.42%, respectively. The level of dCl for optimized feed intake (FI; $p{\leq}0.006$), FG ($p{\leq}0.007$) and litter moisture (LM; $p{\leq}0.001$) was observed at 0.60%, 0.38% and 0.73%, respectively, for d 1 to 42. Water intake (DWI) was not affected by increasing dCl supplementation (p>0.05); however, the ratio between DWI and FI (DWI:FI) was found highest at 0.73% dCl during d 1 to 10 ($p{\leq}0.05$) and d 21 to 33 ($p{\leq}0.009$). Except for d 34 to 42 ($p{\leq}0.006$), the increasing level of dCl did not result in a significant difference in mortality during any phase. Blood pH and glucose, and breast and thigh weights (percentage of dressed weight) were improved while dressing percentage (DP) and gastrointestinal health were exacerbated with $NH_4Cl$ as compared to $CaCl_2$ supplemented diets ($p{\leq}0.001$). Higher plasma $Na^+$ and $HCO_3{^-}$ and lower $Cl^-$ and $Ca^{{+}{+}}$ were observed in $NH_4Cl$ supplemented diets ($p{\leq}0.001$). Increasing supplementation of dCl increased plasma $Cl^-$ ($p{\leq}0.04$; quadratically) and linearly reduced plasma $K^+$ ($p{\leq}0.001$), $Ca^{{+}{+}}$ ($p{\leq}0.003$), $HCO_3{^-}$ ($p{\leq}0.001$), and $Na^+$ ($p{\leq}0.001$; quadratically). Consequently, higher requirements of dietary chloride are suggested for feed intake; nevertheless, lower levels of dietary chloride are sufficient to support optimal BWG and FG with increasing age. The $NH_4Cl$ supplemented diets ameliorate breast and thigh meat yield along with overall energy balance (glucose).
Outlines for plasma $estradiol-17\beta$, components, electrophoretic patterns, and ultrastructural changes were obtained in female rainbow trout (Oncorhynchus mykiss) during the seasonal reproductive cycles. Plasma $estradiol-17\beta$ under the natural conditions, exhibited distinct seasonal variation, peaking very late in vitellogenic season during September, decreasing gradually the halt of spawning in December, and ultimately falling during the early stages of seasonal ovarian recrudescence in February and March. This change in $estradiol-17\beta$ appeared to stimulate vitellogenin production as evidenced by increases in plasma calcium, phosphorus, glucose, albumin and total protein levels. The electrophoretic patterns of late maturing or spawning oocytes were stained more intensively than those of late perinucleolus oocytes (molecular weights of approximately 70,000 and 200,000). Two protein bands were found in the SDS-PAGE separation, coincident with the $estradiol-17\beta$ hormone peak. Gonadosomatic indices (GSI) significantly increased from October to January, and showed the highest peak in January, coinciding with the numerically abrupt increase of ripe ova in female. A positive correlation (r=0.701, p<0.01) was established between plasma $estradiol-17\beta$ levels and the gonadosomatic index during the prespawning. The highest level of hepatosomatic index (HSI) observed in December. During the breeding season (December), the gonadotropes were large and filled with GTH-containing inclusions such as granules and globules. The vitellogenic phase began as late perinurleolus oocytes became transformed into early maturing oocytes through the accumulation of yolk, and oocytes reached the late maturing stages as the ooplasm was completely packed with yolk. Marked ultrastructural changed in the granulosa cells during nuclear migration involve the dilation of the rough endoplasmic reticulum and the appearance of the rod-shaped mitochondria with tubular cristae. Microvilli (finger-like projections), from the zona radiata and from the oocyte grew, and made contact with each other in the pore canals of the zona radials during vitellogenesis, but were withdrawn as the zona radiata became more compact and devoid of pore canals during oocyte maturation. The zona radiata grew to a tripartite structure such as an outer thin homogeneous layer, and two inner thick helicoidal layers (zona radials interna and zona radiata externa). Under the normal conditions, the ovarian follicle influenced the histological development and periodical secretion of the hormones , sufficient for a oogenesis and gonadal steroid production.
We evaluated the effects of rice distillers dried grain (DDG) as a partial replacement for fish meal in the practical diet on growth performance, feed utilization, and body composition of juvenile olive flounder Paralichthys olivaceus. Six isonitrogenous and isocaloric diets were formulated to contain 0%, 7%, 14%, 21%, 28%, and 35% DDG (designated DDG0, DDG7, DDG14, DDG21, DDG28, and DDG35, respectively). Three replicate groups of juvenile olive flounder averaging $9.6{\pm}0.2g$ were fed one of the experimental diets to visual satiety twice daily for 8 weeks. Neither survival nor daily feed intake was affected by the dietary DDG levels. Weight gain of the flounder fed the DDG28 and DDG35 diets was lower than that of flounder fed the DDG7 diet. The feed efficiency of flounder fed the DDG28 diet was lower than that of flounder fed the DDG0, DDG7, and DDG14 diets. The protein efficiency ratio of flounder fed the DDG28 diet was lower than that of flounder fed the DDG7 diet. The proximate composition of muscle was not affected by the dietary DDG levels. The plasma contents of total protein, glucose, cholesterol, glutamate oxaloacetate transaminase, phospholipid, and triglyceride were not affected by the dietary DDG levels. The results of this experiment suggest that DDG has the potential to replace fish meal and could be used up to 21% DDG without any negative effects on the growth and feed utilization of juvenile flounder.
High-protein fermented whey beverage (FWB) was manufactured using whey protein concentrate (WPC) and Lactobacillus plantarum DK211 isolated from kimchi. This study was designed to evaluate the anti-obesity activity of FWB in male rats fed a high-fat diet. Male Sprague-Dawley rats were randomly assigned to three groups (n=8 per group). The three groups differed in their diet; one group received a normal diet (ND), another, a high-fat diet (HD), and the third, a HD plus fermented whey beverage (HDFWB), for 4 wk. Supplementation with FWB (the HDFWB group) prevented weight gain and body fat accumulation. The food intake in the HDWFB group was significantly lower (p<0.05) than that of the HD group. The HDWFB group also showed a significant decrease in organ weights (p<0.05), except for the weight of the testis. There was a significant decrease in total cholesterol, LDL-cholesterol, and triglycerides in the HDFWB group compared with the HD group (p<0.05), but there was no significant difference in serum HDL-cholesterol levels among the experimental groups. Rats ingesting FWB (the HDFWB group) also showed a significant decrease in blood glucose levels, and plasma levels of insulin, leptin, and ghrelin compared to HD group (p<0.05). These results indicate that FWB has beneficial effects on dietary control, weight control, and reduction in fat composition and serum lipid level; consequently, it may provide antiobesity and hypolipidemic activity against high fat diet-induced obesity in rats.
In this study. the importance of body fat distribution as an indicator of metabolic aberrations in diabetics was'evaluated. Skinfold thicknesses at eight sites and circumferences at five sites and total body fat content were measured on 105 diabetics. 1) The waist/thigh girth ratio(WTR) was positively correlated(r=0.38-0.54) to plasma glucose levels during oral glucose loading in diabetic men alone. 2) There was no significant difference in serum total cholesterol of diabetics and nondiabetics. However, HDL-cholesterol was significantly lower(p : 0.000. in male and female) in diabetics(male : 36.31$\pm$ 16.98mg/dl, female: 37.89$\pm$14.67mg/dl) than nodiabetics(male 61.75$\pm$14.08mg/dl, female : 62.29$\pm$12.65mg/dl) and serum triglyceride was significantly higher(p=0.0212) in diabetic women(171.90$\pm$ 76.61mg/dl) than nondiabetic women(111.10$\pm$42.84mg/dl) . 3) In both sexes. anthropometric measurements that significantly correlated to serum triglyceride concentration were percentage of ideal body weight. body mass index(BMI) and waist circumference. Positive and significant correlations were found between serum cholestrol, and BMI(R: 0.31, 0.34) and waist circumference(r=0.29) in diabetic men. Moreover, skinfolds of trunk area(r=0.29~0.32) especially abdomen, were closely associated with serum lipids than other fat deposits. Increasing percentage of total body fat content was accompanied by progressively increasing serum triglyceride concentration(r=0.41) in dieabetic men. This study shows that knowledge of body fat localization may help identify risks of carbohydrate intolerance and hyperlipidemia in diabetics.
The aim of this study was to determine whether the addition of soy isoflavones to dairy ice cream modifies diabetic biomarkers in the type 2 diabetic model mice. Forty male C57BL/6J-ob/ob mice were randomly divided into 4 groups and fed control diet (basal, 7% fat), MS diet (milk ice cream with sugar, 20% fat), MS-SI diet (MS ice cream with 0.01% soy isoflavones, 20% fat), or MF-SI diet (milk ice cream with 0.01% soy isoflavones, 5% fructooligosaccharide, 20% fat) for 12 weeks. Blood response area by glucose tolerance test, plasma levels of glucose, insulin, C-peptide, leptin, and blood $HbA_{1c}$ were not significantly different among all the groups. Concentrations of interleukin-6 and tumor necrosis factor-${\alpha}$ secreted from splenocytes induced by Concanavalin A were not significantly different among all the groups. In conclusion, soy isoflavones supplemented to ice cream did not alter diabetic biomarkers in diabetic type 2 model mice.
Purpose: To analyze the differences of the Body Mass Index (BMI), blood biochemical indices (TC, TG, HDL, PP2) among college faculty members depending on their life styles and thereupon, provide for some basic data useful for healthcare education. Methods: 163 faculty members were sampled for a questionnaire survey and a medical checkup, both conducted from Jan. 20 to Jan. 26, 2010. Results: First, such blood biochemical indicesas BMI, TG, HDL and PP2 differed significantly depending on gender, while TC, TG and HDL differed significantly depending on age. Second, BMI differed significantly depending on drinking. Third, smokers showed significantly lower BMI and PP2 than non-smokers. Among the smokers, those smoking for 1-10 years showed a significantly lower level of TG. Fourth, those exercising as hard as sweating 3 times a week showed significantly lower BMI, TC and TG. Fifth, BMI was correlated positively with TC and TG, while being correlated negatively with HDL. On the other hand, TC was correlated positively with the TG which was correlated negatively with the HDL which was correlated positively with PP2. Conclusion: In order to prevent chronic diseases and live a healthy life, it must be necessary to control drinking, stop smoking and exercise regularly.
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