Glucose-regulating Enzyme Activities Research Articles

Oral Administration of Germinated, Pigmented, Giant Embryo Rice (Oryza sativa L. cv. Keunnunjami) Extract Improves the Lipid and Glucose Metabolisms in High-Fat Diet-Fed Mice.

Obesity is a significant risk factor for chronic diseases. The effect of ethanol extract from germinated Keunnunjami, blackish-purple rice with a giant embryo, compare to ordinary brown rice, on the body weight and lipid and glucose metabolism in high-fat diet-fed mice was analyzed. Mice were fed with a high-fat diet-fed for 3 weeks and then orally administered with either distilled water (HF) or extract (0.25%, w/w) from brown, germinated brown, Keunnunjami, and germinated Keunnunjami rice for 4 weeks. Control mice were fed with a normal diet and orally administered with distilled water. The HF group showed markedly higher body weight and triglyceride, cholesterol, fatty acid, glucose, and insulin levels than the control group. However, the oral administration of rice extracts ameliorated this high-fat diet-induced obesity, hyperlipidemia, and hypoglycemia through the modulation of adipokine production, lipogenic and glucose-regulating enzyme activities, and mRNA expression of genes associated with lipid and glucose metabolism. The germinated Keunnunjami extract exhibited greater hypolipidemic, hypoglycemic, and body weight-lowering effects than the other rice extracts. The results demonstrated that germination could further enhance the physiological properties of rice and that germinated Keunnunjami extract has a strong therapeutic potential against high-fat diet-induced obesity, hyperlipidemia, and hyperglycemia.

Anti-diabetic effects of blue honeyberry on high-fed-diet-induced type II diabetic mouse.

BACKGROUND/OBJECTIVEThe blue honeysuckle berry (Lonicera caerulea var. edulis L.) is a small deciduous shrub belonging to the Caprifoliaceae family that is native to Russia, China, Japan, and Korea. The berry of this shrub is edible, sweet and juicy and is commonly known as the blue honeyberry (BHB). This study examined the anti-diabetic potential of BHB on high-fat-diet-induced mild diabetic mice. The hypoglycemic, and nephroprotective effects of the 12-week oral administration of blue honeyberry extract were analyzed.MATERIALS/METHODSThe hypoglycemic effects were based on the observed changes in insulin, blood glucose, and glycated hemoglobin (HbA1c). Furthermore, the changes in the weight of the pancreas, including its histopathology and immunohistochemical investigation were also performed. Moreover, the nephroprotective effects were analyzed by observing the changes in kidney weight, its histopathology, blood urea nitrogen (BUN), and serum creatinine levels.RESULTSThe results showed that the high-fat diet (HFD)-induced control mice showed a noticeable increase in blood glucose, insulin, HbA1c, BUN, and creatinine levels. Furthermore, growth was observed in lipid droplet deposition related to the degenerative lesions in the vacuolated renal tubules with the evident enlargement and hyperplasia of the pancreatic islets. In addition, in the endocrine pancreas, there was an increase in the insulin-and glucagon-producing cells, as well as in the insulin/glucagon cell ratios. On the other hand, compared to the HFD-treated mice group, all these diabetic and related complications were ameliorated significantly in a dose-dependent manner after 84 days of the continuous oral administration of BHBe at 400, 200 and 100 mg/kg, and a dramatic resettlement in the hepatic glucose-regulating enzyme activities was observed.CONCLUSIONSBy assessing the key parameters for T2DM, the present study showed that the BHBe could act as a potential herbal agent to cure diabetes (type II) and associated ailments in HFD-induced mice.

Blood glycemia-modulating effects of melanian snail protein hydrolysates in mice with typeII diabetes.

Freshwater animal proteins have long been used as nutrient supplements. In this study, melanian snail (Semisulcospira libertina) protein hydrolysates (MPh) were found to exert anti-diabetic and protective effects against liver and kidney damage in mice with type II diabetes adapted to a 45% kcal high-fat diet (HFD). The hypoglycemic, hepatoprotective and nephroprotective effects of MPh were analyzed after 12 weeks of the continuous oral administration of MPh at 125, 250 and 500 mg/kg. Diabetic control mice exhibited an increase in body weight, and blood glucose and insulin levels, with a decrease in serum high-density lipoprotein (HDL) levels. In addition, an increase in the regions of steatohepatitis, hepatocyte hypertrophy, and lipid droplet deposit-related renal tubular vacuolation degenerative lesions were detected, with noticeable expansion and hyperplasia of the pancreatic islets, and an increase in glucagon- and insulin-producing cells, insulin/glucagon cell ratios in the endocrine pancreas and hepatic lipid peroxidation, as well as decreased zymogen contents. Furthermore, a deterioration of the endogenous antioxidant defense system was observed, with reduced glucose utilization related hepatic glucokinase (GK) activity and an increase in hepatic gluconeogenesis-related phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6pase) activity. However, all of these diabetic complications were significantly inhibited by oral treatment with MPh in a dose-dependent manner. In addition, the marked dose-dependent inhibition of hepatic lipid peroxidation, the depletion of the liver endogenous antioxidant defense system, and changes in hepatic glucose-regulating enzyme activities were also observed. The results of this study suggest that MPh exerts potent anti-diabetic effects, along with the amelioration of related complications in mice with type II diabetes. The overall effects of MPh at a dose of 125 mg/kg on HFD-induced diabetes and related complications were similar or more potent than those of metformin (250 mg/kg).

두충 열수추출물 급여에 의한 갱년기 유도 모델 흰쥐의 지질, 당질 및 항산화 대사 개선에 미치는 영향

In postmenopausal women, estrogen deficiency can be associated with metabolic diseases, such as obesity, diabetes, and cardiovascular diseases. The purpose of this study was to investigate factors related to lipid, glucose and antioxidnat metabolism. Sprague-Dawley female rats were subjected to either bilateral ovariectomy or sham operation and randomly divided into 3 dietary groups, (n=8) sham-operated fed with normal diet (SHAM), ovariectomized fed with normal diet (OVX), and ovariectomized fed with normal diet supplemented with Eucommia ulmoides extract (OVX-EU). The OVXEU group showed significantly lower body weight, triacylglycerol, and total cholesterol than that showed by the OVX group. In addition, the OVX-EU group showed improved lipogenesis, glucose-regulating enzyme activities, adipokine and antioxidant enzyme activities. These findings demonstrate that extracts from E. ulmoides extract can be used as a functional food.

Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi) Improves Glucose and Bone Metabolisms in Ovariectomized Rats.

The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10): normal control diet (NC) and normal diet supplemented with non-germinated Superhongmi (SH) or germinated Superhongmi (GSH) rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-β-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance.

Aged ginseng (Panax ginseng Meyer) reduces blood glucose levels and improves lipid metabolism in high fat diet-fed mice.

Aged ginseng is unpeeled ginseng root that has been dried and heat-treated in an oven at 80°C for 14 days. The effects of aged ginseng, in comparison with white and red ginseng, on the lipid and glucose metabolism in high fat-fed mice were investigated. C57BL/6N mice were randomly divided into six dietary groups of normal control, high fat, and high fat supplemented with white, red, aged four-year old, and aged five-year old ginseng. After 8 weeks, ginseng counteracted high fat dietinduced body weight gain, hyperlipidemia, and hyperglycemia via a mechanism involving modulation of hepatic lipogenesis, adipokine production, and glucose-regulating enzyme activities. Aged ginseng showed greater antihyperlipidemic and antihyperglycemic activities than white ginseng and exhibited physiological effects similar to red ginseng, perhaps due to a relatively high ginsenoside content. Aged ginseng can be beneficial as a functional food.

Modulatory effects of morin on hyperglycemia by attenuating the hepatic key enzymes of carbohydrate metabolism and β-cell function in streptozotocin-induced diabetic rats

The present study was aimed to evaluate the effect of morin on blood glucose, insulin level, hepatic glucose regulating enzyme activities and glycogen level in experimental diabetes. Diabetes mellitus was induced by a single intraperitoneal injection of streptozotocin (STZ) (50mg/kg b.w.). Five days after STZ injection, diabetic rats received morin (25 and 50mg/kg b.w.) orally for 30 days. Glibenclamide was used as reference drug. Morin treatment significantly reduced the blood glucose and improved the serum insulin levels. Further, a dose-dependent reduction in glucose-6-phosphatase and fructose-1,6-bisphosphatase was observed along with the increase in liver hexokinase and glucose-6-phosphate dehydrogenase activities. Morin supplement were found to be effective in preserving the normal histological appearance of pancreatic islets as well as to preserve insulin-positive β-cells in STZ-rats. Therefore, these findings suggest that morin displays beneficial effects in the treatment of diabetes, mediated through the regulation of carbohydrate metabolic enzyme activities.

Platycodi radix saponin inhibits α-glucosidase in vitro and modulates hepatic glucose-regulating enzyme activities in C57BL/KsJ-db/db mice

This study investigated anti-diabetic activity of a concentrated saponin fraction from Platycodi radix (SK1) in C57BL/KsJ-db/db mice and its underlying mechanism. Mice were fed diet with 0.5 % SK1 (w/w) for 6 weeks. SK1 significantly lowered the blood glucose and glycosylated hemoglobin levels and improved glucose and insulin tolerance. The plasma and pancreatic insulin and C-peptide levels and fecal cholesterol content were increased, whereas plasma urea nitrogen, free fatty acid and triglyceride levels were decreased by SK1 supplementation. Glucokinase (GK) activity in the liver was significantly higher in the SK1 group than the control group, whereas the glucose-6-phosphatase (G6Pase) activity was lower. SK1 significantly down-regulated GK mRNA expression compared to the control group but did not affect G6Pase and glucose transporter 2 mRNA. Phosphoenolpyruvate carboxykinase activity and mRNA levels did not differ between groups. SK1 also markedly inhibited the small intestinal disaccharidases activities compared to those of control db/db mice. Furthermore, SK1 was a more effective α-glucosidase inhibitor than acarbose in vitro. Overall, these findings suggest that SK1 is a potential glucose-lowering agent that functions via inhibition of carbohydrate digestive enzyme activities and modulation of glucose-regulating enzyme activities in db/db mice.

Antihyperglycemic and antioxidative effects of Hydroxyethyl Methylcellulose (HEMC) and Hydroxypropyl Methylcellulose (HPMC) in mice fed with a high fat diet.

The effect of dietary feeding of hydroxyethyl methylcellulose (HEMC) and hydroxypropyl methylcellulose (HPMC) on the glucose metabolism and antioxidative status in mice under high fat diet conditions was investigated. The mice were randomly divided and given experimental diets for six weeks: normal control (NC group), high fat (HF group), and high fat supplemented with either HEMC (HF+HEMC group) or HPMC (HF+HPMC group). At the end of the experimental period, the HF group exhibited markedly higher blood glucose and insulin levels as well as a higher erythrocyte lipid peroxidation rate relative to the control group. However, diet supplementation of HEMC and HPMC was found to counteract the high fat-induced hyperglycemia and oxidative stress via regulation of antioxidant and hepatic glucose-regulating enzyme activities. These findings illustrate that HEMC and HPMC were similarly effective in improving the glucose metabolism and antioxidant defense system in high fat-fed mice and they may be beneficial as functional biomaterials in the development of therapeutic agents against high fat dietinduced hyperglycemia and oxidative stress.

Effects of brown alga, Ecklonia cava on glucose and lipid metabolism in C57BL/KsJ-db/db mice, a model of type 2 diabetes mellitus

Recently, there has been a growing interest in alternative therapies of marine algae for diabetes. Therefore, the anti-diabetic effects of brown alga, Ecklonia cava was investigated in type 2 diabetic animal. Male C57BL/KsJ-db/db (db/db) mice were divided into control, dieckol rich extract of E. cava (AG-dieckol), or rosiglitazone (RG) groups. The blood glucose, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the AG-dieckol and RG groups than in the control db/db mice group, while glucose tolerance was significantly improved in the AG-dieckol group. AG-dieckol markedly lowered plasma and hepatic lipids concentration compared to the control db/db mice group. The antioxidant enzyme activities were significantly higher in the AG-dieckol group than in the control db/db mice group, yet its TBARS level was markedly lower compared to the RG group. With regard to hepatic glucose regulating enzyme activities, glucokinase activity was enhanced in the AG-dieckol group mice, while glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities in the AG-dieckol group mice were significantly lowered than those in the control db/db mice group. These results suggest that AG-dieckol exert an anti-diabetic effect in type 2 diabetic mice by improving the glucose and lipid metabolism and antioxidant enzymes.

Effects of Phytoestrogens on Glucose Metabolism in C57BL/KsOlaHsd-db/db Mice

This study was conducted to evaluate the antihyperglycemic effects of three phytoestrogens, genistein, coumestrol, and enterolactone, in type 2 diabetic animals. Forty male C57BL/KsOlaHsd-db/db mice were used as a diabetic animal model. The animals were divided into four groups and fed a phytoestrogen-free AIN-76 diet (control), or one of three phytoestrogen-supplemented (3.75 mg/100 g diet) AIN-76 diets for six weeks. During the experimental period, fasting blood glucose levels were measured on week 0, 2, 5, and 6 of the experiment, and oral glucose tolerance tests were performed on the 5th week. After the experimental period, blood concentrations of HbA1c, insulin, and glucagon were measured, and hepatic glycogen content and glucose regulating enzyme activities were analyzed. Fasting blood glucose, HbA1c level, and the area under the blood glucose curve in the oral glucose tolerance test were significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Plasma glucagon levels were also significantly lower in all of the phytoestrogen-supplemented groups compared to the control group. Hepatic glycogen level was significantly higher in the coumestrol-supplemented group compared to the other groups. However, there were no significant differences in the activities of glucokinase and glucose-6-phosphatase between the groups. These results suggest that all of the three major phytoestrogens tested in the present study were effective in lowering blood glucose levels in type 2 diabetic animals. However, further studies need to be conducted to elucidate the exact mechanism for the hypoglycemic effects of phytoestrogens. (Korean J Nutr 2011 44(4): 275 ~ 283)

Effect of Oryzanol and Ferulic Acid on the Glucose Metabolism of Mice Fed with a High‐Fat Diet

The effects of oryzanol and ferulic acid on the glucose metabolism of high-fat-fed mice were investigated. Male C57BL/6N mice were randomly divided into 4 groups: NC group fed with normal control diet; HF group fed with high-fat (17%) diet; HF-O group fed with high-fat diet supplemented with 0.5% oryzanol; and HF-FA group fed with high-fat diet supplemented with 0.5% ferulic acid. All animals were allowed free access to the experimental diets and water for 7 wk. At the end of the experimental period, the HF-O and HF-FA groups exhibited significantly lower blood glucose level and glucose-6-phosphatase (G6pase) and phosphoenolpyruvate carboxykinase (PEPCK) activities, and higher glycogen and insulin concentrations and glucokinase (GK) activity compared with NC and HF groups. The results of this study illustrate that both oryzanol and ferulic acid could reduce the risk of high-fat diet-induced hyperglycemia via regulation of insulin secretion and hepatic glucose-regulating enzyme activities.

Modulatory Effect of Rice Bran and Phytic Acid on Glucose Metabolism in High Fat-Fed C57BL/6N Mice

The effect of dietary feeding of rice bran and phytic acid on the glucose metabolism in high fat-fed C57BL/6N mice fed was investigated. The mice were given with either a high fat diet only (HF group) or a high fat diet supplemented with rice bran (HF-RB group) or phytic acid (HF-PA group) for 7 weeks. The control mice (NC group) received a normal diet. At the end of the experimental period, the HF group exhibited substantially higher blood glucose level than the NC group. However, the HF-RB and HF-PA groups showed a marked decrease in the blood glucose level relative to HF mice. Furthermore, significantly higher glucokinase (GK) activity and lower phosphoenolpyruvate carboxykinase (PEPCK) activity were observed in HF-RB and HF-PA mice compared with that of the NC and HF ones. It was also found that the glucose-6-phosphatase (G6pase) activity and hepatic glycogen concentration were considerably higher in HF-RB and HF-PA groups, respectively, than that of the HF mice. These findings demonstrate that both rice bran and phytic acid could reduce the risk of high fat diet-induced hyperglycemia via regulation of hepatic glucose-regulating enzyme activities.

Dietary Hesperidin Exerts Hypoglycemic and Hypolipidemic Effects in Streptozotocin-Induced Marginal Type 1 Diabetic Rats

Citrus bioflavonoids may offer some protection against the early stage of diabetes mellitus and the development of complications. We investigated the effect of hesperidin on blood glucose levels, hepatic glucose-regulating enzyme activities, serum insulin and adiponectin levels, serum and hepatic lipid levels, and parameters of bone loss in streptozotocin (STZ)-induced marginal type 1 diabetic rats. Weanling male rats were randomly assigned to experimental 3 groups: a control (C) group, a STZ induced marginal type 1 diabetes (S) group, and a diabetes and hesperidin group, and fed their respective diets for 4 weeks. STZ injection increased blood glucose in rats, but the increase was marginal. Serum and hepatic lipids, serum adiponectin and insulin levels were significantly changed by STZ injection. Dietary hesperidin (10 g/kg diet) decreased blood glucose by altering the activity of glucose-regulating enzymes, and normalized the lipids and adiponectin levels, but did not change bone parameters in the marginal type 1 diabetic rats. Hesperidin showed both hypoglycemic and hypolipidemic effects but did not affect bone tissue and bone metabolic makers in STZ-injected marginal diabetic weanling rats without any body weight loss due to STZ injection.

Effect of curcumin supplementation on blood glucose, plasma insulin, and glucose homeostasis related enzyme activities in diabetic db/db mice

We investigated the effect of curcumin on insulin resistance and glucose homeostasis in male C57BL/KsJ-db/db mice and their age-matched lean non-diabetic db/+ mice. Both db/+ and db/db mice were fed with or without curcumin (0.02%, wt/wt) for 6 wks. Curcumin significantly lowered blood glucose and HbA 1c levels, and it suppressed body weight loss in db/db mice. Curcumin improved homeostasis model assessment of insulin resistance and glucose tolerance, and elevated the plasma insulin level in db/db mice. Hepatic glucokinase activity was significantly higher in the curcumin-supplemented db/db group than in the db/db group, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxykinase activities were significantly lower. In db/db mice, curcumin significantly lowered the hepatic activities of fatty acid synthase, beta-oxidation, 3-hydroxy-3-methylglutaryl coenzyme reductase, and acyl-CoA: cholesterol acyltransferase. Curcumin significantly lowered plasma free fatty acid, cholesterol, and triglyceride concentrations and increased the hepatic glycogen and skeletal muscle lipoprotein lipase in db/db mice. Curcumin normalized erythrocyte and hepatic antioxidant enzyme activities (superoxide dismutase, catalase, gluthathione peroxidase) in db/db mice that resulted in a significant reduction in lipid peroxidation. However, curcumin showed no effect on the blood glucose, plasma insulin, and glucose regulating enzyme activities in db/+ mice. These results suggest that curcumin seemed to be a potential glucose-lowering agent and antioxidant in type 2 diabetic db/db mice, but had no affect in non-diabetic db/+ mice.

Effects of the ethanol extract of the roots of Brassica rapa on glucose and lipid metabolism in C57BL/KsJ- db/db mice

The antidiabetic efficacy of turnip (Brassica rapa) roots ethanol extract (TE) was investigated in type 2 diabetic animals. C57BL/KsJ-db/db (db/db) mice and db/+ mice were used and the db/db mice were divided into control, TE (0.26 g/100g diet) and rosiglitazone (RG, 0.005 g/100g diet) groups. Despite hyperinsulinemia, the glucokinase activity was lower in the liver of the db/db mice than the db/+ mice, while the glucose-6-phosphatase activity was higher. TE and RG improved the glucose and insulin tolerance and lowered the blood glycosylated hemoglobin, plasma insulin, C-peptide and glucagon levels as well as reversed these hepatic glucose regulating enzyme activities in db/db mice. TE also increased the insulin/glucagon ratio and hepatic glycogen content. The plasma free fatty acid and plasma and hepatic cholesterol and triglyceride levels were higher in the db/db mice than db/+ mice. Interestingly, TE and RG lowered these plasma and hepatic lipids, and simultaneously reduced the hepatic phosphatidate phosphohydrolase, HMG-CoA reductase, ACAT, beta-oxidation and carnitine palmitoyl transferase activities. Furthermore, TE lowered the hepatic fatty acid synthase activity, hepatic lipid droplets accumulation, and adipose tissue weight and size. We suggest TE may exert an antidiabetic effect in type 2 diabetic mice by enhancing the glucose and lipid metabolism.

Galacto-oligosaccharides and bowel function

Background: Menopause induces various metabolic disorders due to the rapid decrease of the ovarian hormone estrogen. It is involved in increased risk of obesity, diabetes, dyslipidemia, and osteoporosis. The pigmented giant embryo cultivar is a promising food product for menopause-induced metabolic disorders. Objective: The effects of non-germinated and germinated Keunnunjami, a new blackish purple pigmented rice with a giant embryo, on glucose and bone metabolisms in ovariectomized rats were investigated. Design: The animals were fed with normal control diet (NC group) or control diet supplemented with either non-germinated Keunnunjami (KN group) or germinated Keunnunjami (GKN group) powder for 8 weeks. Results: The blood glucose and plasma insulin levels, adipokine concentrations, hepatic glucose-regulating enzyme activities, and bone resorption biomarker levels significantly decreased in KN and GKN groups compared to those of the control animals. Discussion: These findings illustrate that GKN group showed greater hypoglycemic activity and lower bone resorption than KN group, suggesting that germination could further improve the physiological property of Keunnunjami. Conclusion: Germinated Keunnunjami may have therapeutic potential against hyperglycemia and bone turnover imbalance caused by menopause.

The anti-diabetic effects of ethanol extract from two variants of Artemisia princeps Pampanini in C57BL/KsJ- db/ db mice

The anti-diabetic effects of two variants of Artemisia princeps Pampanini, sajabalssuk (SB) and sajuarissuk (SS), were investigated in type 2 diabetic animal using their ethanol extracts. Male C57BL/KsJ- db/ db ( db/ db) mice were divided into control, SB ethanol extract (SBE), SS ethanol extract (SSE), or rosiglitazone (RG) groups and their age-matched littermates ( db/+) were used. Supplementation of the SBE (0.171 g/100 g diet), SSE (0.154 g/100 g diet), and RG (0.005 g/100 g diet) improved glucose and insulin tolerance and significantly lowered blood glycosylated hemoglobin levels, as compared to the control group. Plasma insulin, C-peptide and glucagon levels in db/ db mice were higher in the db/+ mice, however these values were significantly lowered by SBE, SSE or RG-supplement. Hepatic GK activity was significantly lower in the db/ db mice than in the db/+ mice, while hepatic G6Pase activity was vice versa. Supplementation of SBE, SSE and RG reversed these hepatic glucose-regulating enzyme activities. In addition, SBE and SSE markedly increased the hepatic glycogen content and muscle ratio as compared to the control group, but they did not alter the food intake, body weight and plasma leptin level. The RG group, however, showed a significant increase in the food intake, body weight and plasma leptin. These results suggest that SBE and SSE exert an anti-diabetic effect in type 2 diabetic mice.