• The Korean Journal of Physiology and Pharmacology
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• v.19 no.3
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• pp.197-202
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• 2015

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with $30{\mu}g$ of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

• YAKHAK HOEJI
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• v.52 no.5
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• pp.345-354
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• 2008

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.

• Nutrition Research and Practice
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• v.2 no.4
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• pp.283-288
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• 2008

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.

• The Korean Journal of Pharmacology
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• v.29 no.2
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• pp.253-261
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• 1993

Possible changes in the role of insulin-sensitive cyclic nucleotide phosphodiesterase(PDE) in mediating the antilipolytic action of insulin were investigated in adipocytes from streptozotocin-induced diabetic rats. Isolated adipocytes prepared from epididymal adipose tissue were incubated, with or without insulin, at $37^{\circ}C$ for 15 min following pretreatment with various drugs or toxins, and three (plasma membranes, microsomal membranes, and cytosol) fractions prepared by differential centrifugation were then assayed for cAMP phosphodiesterase activity. The PDE activities only in the crude microsomal (P2) fractions were activated by insulin both in diabetic and control rats. The basal PDE activities in P2 fractions of adipocytes from diabetic rats were higher than those from control rats, although the maximal effects observed at 2 nM of insulin, $100\;{\mu}M$ of isoproterenol or the combination of both were not significantly different from each other. The insulin-stimulated PDE activities in P2 fractions of adipocytes from diabetic rats were not changed by PIA, a $A_{1}$ adenosine receptor agonist, whereas they were decreased to the basal PDE activities in those from control rats. In addition, the adipocytes from diabetic rats showed an increased sensitivity to pertussis toxin compared to those from controls. There were no differences between diabetic and control rats in the sensitivity of adipocytes to cholera toxin. These data indicate that the impaired signalling through inhibitory receptors such as adenosine receptors in adipocytes from streptozotocin-induced diabetes relates to the loss or the decreased function of $G_i$ proteins, and leads to the increased activity of the insulin-dependent PDE at the basal states.

• Nutrition Research and Practice
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• v.4 no.6
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• pp.492-498
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• 2010

Both metabolic syndrome (MetS) and elevated LDL cholesterol (LDL-C) increase the risk for cardiovascular disease (CVD). We hypothesized that low HDL cholesterol (HDL-C) would further increase CVD risk in women having both conditions. To assess this, we recruited 89 women with MetS (25-72 y) and LDL-C ${\geq}$ 2.6 mmol/L. To determine whether plasma HDL-C concentrations were associated with dietary components, circulating atherogenic particles, and other risk factors for CVD, we divided the subjects into two groups: high HDL-C (H-HDL) (${\geq}$ 1.3 mmol/L, n=32) and low HDL-C (L-HDL) (< 1.3 mmol/L, n=57). Plasma lipids, insulin, adiponectin, apolipoproteins, oxidized LDL, Lipoprotein(a), and lipoprotein size and subfractions were measured, and 3-d dietary records were used to assess macronutrient intake. Women with L-HDL had higher sugar intake and glycemic load (P< 0.05), higher plasma insulin (P< 0.01), lower adiponectin (P< 0.05), and higher numbers of atherogenic lipoproteins such as large VLDL (P < 0.01) and small LDL (P<0.001) than the H-HDL group. Women with L-HDL also had larger VLDL and both smaller LDL and HDL particle diameters (P<0.001). HDL-C was positively correlated with LDL size (r=0.691, P<0.0001) and HDL size (r=0.606, P<0.001), and inversely correlated with VLDL size (r=-0.327, P<0.01). We concluded that L-HDL could be used as a marker for increased numbers of circulating atherogenic lipoproteins as well as increased insulin resistance in women who are already at risk for CVD.

• Nutrition Research and Practice
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• v.8 no.2
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• pp.177-182
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• 2014

BACKGROUND/OBJECTIVES: Irisin, a newly identified hormone, is associated with energy homeostasis. We investigated whether aged garlic extract (AGE) and exercise training intervention could improve body weight, insulin sensitivity, skeletal muscle fibronectin domain containing protein 5 (FNDC-5) levels, and plasma irisin in high-fat diet (HFD). MATERIALS/METHODS: Male Sprague Dawley rats were fed a ND (normal diet, n=5) or HFD (n=28) for 6 weeks. After 6 weeks, all rats were divided into 5 groups for the next 4 weeks: ND, (normal diet, n=5), HFD (high-fat diet, n=7), HFDA (high-fat diet + aged garlic extract, n=7), HFDE (high-fat diet + exercise, n=7), and HFDEA (high-fat diet + exercise + aged garlic extract, n=7). Exercise groups performed treadmill exercises for 15-60 min, 5 days/week, and AGE groups received AGE (2.86 g/kg, orally injected) for 4 weeks. RESULTS: Significant decreases in body weight were observed in the ND, HFDE, and HFDEA groups, as compared with the HFD group. Neither intervention affected the masses of the gastrocnemius muscle or liver. There were no significant differences in glucose levels across the groups. The homeostatic model assessments of insulin resistance were significantly higher in the HFD group, as compared with the ND, HFDA, HFDE, and HFDEA groups. However, skeletal muscle FNDC-5 levels and plasma irisin concentrations were unaffected by AGE or exercise in obese rats. AGE supplementation and exercise training did not affect skeletal muscle FNDC-5 or plasma irisin, which are associated with insulin sensitivity in obese rats. CONCLUSION: Our results suggest that the protection against HFD-induced increases in body fat/weight and insulin resistance that are provided by AGE supplementation and exercise training may not be mediated by the regulation of FNDC-5 or irisin.

• The Korean Journal of Food And Nutrition
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• v.7 no.2
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• pp.108-113
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• 1994

This study was carried out to evaluate the effect of Cnidi rhizoma (CR) water extract on fat accumulation In fatted rats induced by the oral high fat administration for six weeks. To accomplish this evaluation, the serum and liver tissue have been examined for enzyme activity, cortisol and insulin level. The change of liver or tissue have been observed by the light microscope. GOT GPT and LDH activities were lower than the control group. Insulin and cortisol were higher than the control group, due to the fat accumulation. The liver of the control group observed by the tight microscope appeared to the fatty liver, but CR group showed some improvement of the fatty liver Based on the above results, it was shown that it is possible to improve fat accumulation induced by high fat dietary through using the oral administration of Cnidi rhizoma water extract.

• Asian-Australasian Journal of Animal Sciences
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• v.24 no.10
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• pp.1393-1398
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• 2011

Four 4-month old Charolais${\times}$Dorset male sheep (initial liveweight $25.0{\pm}1.1\;kg$), fitted with rumen and abomasal fistulas and nourished by total intragastric infusions, were used to study the relationships between methionine (Met) supply, nitrogen (N) retention and plasma insulin-like growth factor-I (IGF-I). Four graded levels of Met, i.e. 0 g/16 g N, 1.76 g/16 g N, 3.52 g/16 g N and 7.04 g/16 g N, were infused into abomasums as experimental treatments. The sheep and treatments were allocated in a $4{\times}3$ incomplete Latin square design (Yudon square design). The experiment lasted 3 periods and each period was 10 days. Quadratic correlations were found between Met level (x, g/16 g N) and N retention (y, g/d): y = $-0.03x^2$+0.41x+2.62, $r^2$ = 0.66, n = 12, p = 0.008, and between methionine level (x, g/16 g N) and plasma IGF-I concentration (y, ng/ml): y = $0.80x^2$-4.53x+190.24, $r^2$ = 0.51, n = 12, p = 0.009. No significant correlation was found between plasma IGF-I (x, ng/ml) and N retention (y, g/d) (p>0.05). It was concluded that Met level had a significant influence on N retention and plasma IGF-I concentration whereas IGF-I might not be an important mediator in the regulation of N metabolism by Met in growing sheep nourished by total intragastric infusions.

• Nutrition Research and Practice
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• v.5 no.2
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• pp.107-111
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• 2011

The objective of this study was to investigate the hypoglycemic effects of quercetin (QE) in animal models of diabetes mellitus (DM). A starch solution (1 g/kg) with and without QE (100 mg/kg) or acarbose (40 mg/kg) was orally administered to streptozotocin (STZ)-induced diabetic rats after an overnight fast. Postprandial plasma glucose levels were measured and incremental areas under the response curve were calculated. To study the effects of chronic feeding of QE, five-week-old db/db mice were fed an AIN-93G diet, a diet containing QE at 0.08%, or a diet containing acarbose at 0.03% for 7 weeks after 1 week of adaptation. Plasma glucose and insulin, blood glycated hemoglobin, and maltase activity of the small intestine were measured. Oral administration of QE (100 mg/kg) or acarbose (40 mg/kg) to STZ-treated rats significantly decreased incremental plasma glucose levels 30-180 min after a single oral dose of starch and the area under the postprandial glucose response, compared with the control group. QE (0.08% of diet) or acarbose (0.03% of diet) offered to db/db mice significantly reduced both plasma glucose and blood glycated hemoglobin compared to controls without significant influence on plasma insulin. Small intestine maltase activities were significantly reduced by consumption of QE or acarbose. Thus, QE could be effective in controlling fasting and postprandial blood glucose levels in animal models of DM.

• Korean journal of food and cookery science
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• v.16 no.6
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• pp.644-651
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• 2000

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.