• Biomolecules & Therapeutics
• /
• 제13권3호
• /
• pp.190-197
• /
• 2005

Advanced glycation end products (AGE) have been implicated in the pathogenesis of diabetic complications including nephropathy. However, the role of AGE in the activation of mesangial cells cultured under high glucose has not been elucidated. The effects of aminoguanidine, which prevents formation of AGE and protein cross-linking, on the synthesis of $TGF-{\beta}1$ and fibronectin by rat mesangial cells cultured under high glucose for 2 weeks were examined and compared with the effects of $N^G$-nitro-L-arginine methyl ester (NAME), a selective nitric oxide synthase inhibitor, because aminoguanidine also inhibits the inducible nitric oxide synthase. Culture of mesangial cells in 30 mM (high) glucose for 2 weeks induced 1.5-fold (ELISA) and 1.9-fold (Western blot analysis) increase in AGE in the culture media compared to 5.6 mM (control) glucose. Northern blot analysis revealed 1.5-fold increase in $TGF-{\beta}1$ and 1.7-fold increase in fibronectin mRNA expression in cells cultured under high glucose compared to control glucose. Increases in mRNA expression were followed by increased protein synthesis. Mink lung epithelial cell growth inhibition assay revealed 1.4-fold increase in $TGF-{\beta}1$ protein in high glucose media compared to control. Fibronectin protein also increased 2.1-fold that of control glucose by Western blot analysis. Administration of aminoguanidine suppressed AGE formation in a dose dependent manner and at the same time suppressed $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells cultured in both control and high glucose. In contrast, NAME did not affect high glucose-induced changes. These findings support a role for AGE in high glucose-induced upregulation of $TGF-{\beta}1$ and fibronectin synthesis by mesangial cells.

• Journal of Veterinary Science
• /
• 제22권6호
• /
• pp.92.1-92.12
• /
• 2021

Background: Naringin and its aglycone naringenin are citrus-derived flavonoids with several pharmacological effects. On the other hand, the mechanism for the anti-diabetic effects of naringenin and naringin are controversial and remain to be clarified further. Objective: This study examined the relationship between glucose uptake and AMP-activated protein kinase (AMPK) phosphorylation by naringenin and naringin in high glucose-treated HepG2 cells. Methods: Glucose uptake was measured using the 2-NBDG fluorescent D-glucose analog. The phosphorylation levels of AMPK and GSK3β (Glycogen synthase kinase 3 beta) were observed by Western blotting. Molecular docking analysis was performed to evaluate the binding affinity of naringenin and naringin to the γ-subunit of AMPK. Results: The treatment with naringenin and naringin stimulated glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Both flavonoids increased glucose uptake by promoting the phosphorylation of AMPK at Thr172 and increased the phosphorylation of GSK3β. Molecular docking analysis showed that both naringenin and naringin bind to the γ-subunit of AMPK with high binding affinities. In particular, naringin showed higher binding affinity than the true modulator, AMP with all three CBS domains (CBS1, 3, and 4) in the γ-subunit of AMPK. Therefore, both naringenin and naringin could be positive modulators of AMPK activation, which enhance glucose uptake regardless of insulin stimulation in high glucose-treated HepG2 cells. Conclusions: The increased phosphorylation of AMPK at Thr172 by naringenin and naringin might enhance glucose uptake regardless of insulin stimulation in high glucose treated HepG2 cells.

• 대한의생명과학회지
• /
• 제12권3호
• /
• pp.217-224
• /
• 2006

It has been reported that the dysfunctions of podocytes are associated with the development of diabetic nephropathy. In addition, insulin-like growth factors (IGFs) are associated with the development of diabetic nephropathy. However, it is not yet known about the effect of high glucose on IGF-I, -II secretion, and IGF binding proteins (IGFBPs) expression in the podocytes. Thus, this study was conducted to examine the effect of high glucose on IGF system and its involvement of protein kinase C (PKC) and mitogen activated protein kinases (MAPKs) in podocytes. In this study, high glucose (25 mM) increased IGF-I and IGF-II secretion (P<0.05), which was blocked by SB 203580 (a p38 MAPK inhibitor) but not by PD 98059 (a p44/42 MAPK inhibitor). In addition, high glucose-induced stimulation of IGFs was blocked by bisindolylmaleimide I and staurosporine (protein kinase C inhibitors). High glucose also increased IGFBP-l expression, which was blocked by bisindolylmaleimide I and SB 203580. In conclusion, high glucose alters IGFs secretion and IGFBP expression via PKC and p38 MAPK pathways in podocytes.

• Biomolecules & Therapeutics
• /
• 제24권1호
• /
• pp.49-56
• /
• 2016

To determine the protective effect of aloe-emodin (AE) from high glucose induced toxicity in RIN-5F (pancreatic ${\beta}$-cell) cell and restoration of its function was analyzed. RIN-5F cells have been cultured in high glucose (25 mM glucose) condition, with and without AE treatment. RIN-5F cells cultured in high glucose decreased cell viability and increased ROS levels after 48 hr compared with standard medium (5.5 mM glucose). Glucotoxicity was confirmed by significantly increased ROS production, increased pro-inflammatory (IFN-${\gamma}$, IL-$1{\beta}$,) & decreased anti-inflammatory (IL-6&IL-10) cytokine levels, increased DNA fragmentation. In addition, we found increased Bax, caspase 3, Fadd, and Fas and significantly reduced Bcl-2 expression after 48 hr. RIN-5F treated with both high glucose and AE ($20{\mu}M$) decreased ROS generation and prevent RIN-5F cell from glucotoxicity. In addition, AE treated cells cultured in high glucose were transferred to standard medium, normal responsiveness to glucose was restored within 8hr and normal basal insulin release within 24 hr was achieved when compared to high glucose.

• Preventive Nutrition and Food Science
• /
• 제15권1호
• /
• pp.7-13
• /
• 2010

We investigated whether the fermented soymilk extract (FSE) has protective effects against high glucose-induced oxidative stress in human umbilical vein endothelial cells (HUVECs). FSE was prepared via fermentation of soymilk with Bacillus subtilis followed by methanol extraction. To determine the protective effect of FSE, oxidative stress was induced by exposing of HUVECs to the high glucose (30 mM) for 48 hr. Exposure of HUVECs to high glucose for 48 hr resulted in a significant (p<0.05) decrease in cell viability, catalase, SOD and GSH-px activity and a significant (p<0.05) increase in intracellular ROS level and thiobarbituric acid reactive substances (TBARS) formation in comparison to the cells treated with 5.5 mM glucose. However, at concentration of 0.1 mg/mL, FSE treatment decreased intracellular ROS level and TBARS formation, and increased cell viability and activities of antioxidant enzymes including catalase, SOD and GSH-px in high glucose pretreated HUVEC. These results suggest that FSE may be able to protect HUVECs from high glucose-induced oxidative stress, partially through the antioxidative defense systems.

• 한국식품영양학회지
• /
• 제11권5호
• /
• pp.550-555
• /
• 1998

The purpose of this study was to investigate the effects of n-3 polyunsaturated fatty acids(PUFA) on glucose and lipids metabolism in high-fat diet rate. Rats were randomly assigned to normal, high-fat with n-3 PUFA and high-fat dietary groups. Experiments were carried out after 5 weeks feeding with prescriptive diets following 7 hrs fasting. Body weight gains tended to be higher in high-fat fed rats than normal. Blood glucose was increased (p<0.05) by high-fat diet compared with normal diet, and decreaseed (p<0.05) to normal level by n-3 PUFA. Plasma insulin level was significcantly higher (p<0.01) in high-fat diet rats than that of normal-diet rats, and also decreased (p<0.01) by n-3 PUFA. Glucose up take of soleus muscle in vitro was decreased markedly in high-fat fed rats than normal diet rats at 0, 1, 10, and 100nM insulin concentration. Therefore insulin sensitivity and responsiveness were decreased by high-fat diet. Omega-3 PUFA made a recover(p<0.01) insulin sensitivity to almost normal level, and improved (p<0.05) insulin responsiveness in some extent. In conclusion, the results suggest that metabolic disorder of glucose and insulin resistance of skeletal muscle are caused by high-fat diet and n-3 PUFA can ameliorate metabolic disorder and insulin resistance.

• 운동영양학회지
• /
• 제14권2호
• /
• pp.75-80
• /
• 2010

We evaluated the effect of the ginsenoside Re on insulin resistance of glucose transport in muscles of rats made insulin resistant with a high fat diet. After a week of adaptation period to the laboratory environment, 40 male wistar rats were randomly assigned into 2 groups (Chow diet group; CD, n = 20, High fat diet group; HFD, n = 20). After 5-week of high fat diet, Food was removed after 6:00 PM the day before the experiment. The following morning, rats were anesthetized by an intraperitoneal injection of pentobarbital sodium (50 mg/kg body wt), and the soleus muscles were removed. Before incubation, the soleus muscle was split longitudinally into strips with an average weight of 15~20 mg. After the muscle dissection was completed, the abdominal cavity was opened, and the epididymal, mesenteric, and retroperitoneal fat pads were removed and weighed. Treatment of muscles with ginsenoside Re alone had no effect on glucose transport. The high fat diet resulted in ~50% decreases glucose transport rate in soleus muscles. Treatment of muscles with ginsenoside Re in vitro for 90 min completely reversed the high fat diet-induced insulin resistance of glucose transport in soleus muscles. This effect of ginsenoside Re is specific for insulin stimulated glucose transport, as Re treatment did not reverse the high fat diet-induced resistance of skeletal muscle glucose transport to stimulation by contraction. Our results show that the ginsenoside Re induces a remarkably rapid reversal of high fat diet-induced insulin resistance of muscle glucose transport.

• 약학회지
• /
• 제41권6호
• /
• pp.782-788
• /
• 1997

This study was designed to characterize glucose-enhancing effects on endotoxin-induced prostaglandin production in primary cultured rat vascular smooth muscle cells (VSMC). High glucose treatment significantly augmented prostaglandin (PG) synthesis in lipopolysaccharide (LPS)-stimulated VSMC and this effect was maximal at the concentration of 4mg/ml. It has been reported that increases in glucose metabolism through sorbitol pathway could alter the cytosolic $NADH/NAD^+$ ratio and this change favors de novo synthesis of diacylglycerol (DAG) and, in turn. Results in the activation of protein kinase C (PKC) in vascular tissues. Protein kinase C (PKC) inhibitors, staurosporin and H7, blocked the glucose enhancing effect, and DAG, a PKC activator, significantly increased the PG production stimuated by LPS. Sodium pyruvate, which can reverse the alteration in cytosolic NADH/NAD+ ratio, reduced the high glucose effect on PG production. And also, zopolrestat, a strong aldose reductase inhibitor, almost completely blocked the augmentation effect of glucose on PG synthesis. Arachidonic acid release was significantly increased in high glucose treated group, which implied the increase in $PLA_2$ activity was associated with glucose enhancing effect. Metabloic, labeling study clearly showed that de novo synthesis of prostaglandin H synthase-2 (PGHS-2) is greatly increased in high glucose treated group and this was mitigated by the treatment of zopolrestat. Taken together, the activation of PKC through sorbitol pathway increased the activities of $PLA_2$ and PGHS which resulted in the augmentation in LPS-induced PG production in high glucose treated VSMC.

• Journal of Nutrition and Health
• /
• 제33권1호
• /
• pp.59-67
• /
• 2000

The objective of this study was to investigate nutritional status of middle aged Korean men exhibiting impaired glucose tolerance (IGT) and identify the risk factors related to IGT Data were collected from 163 men with a fasting blood glucose level from 115 to 139mg/dl(high blood glucose group: HBG) and 170 men with a normal fasting blood glucose level(control) aged from 40 to 59 years in both groups. Weight, body mass index(BMI) and percent body fat were significantly higher in high blood glucose(HBG) group than those of control group. Age, weight, BMI, percent body fat were positively related to blood glucose. There were no differences in exercise, smoking and family history of diabetes between two groups. Frequency of fat eating and overeating of HBG were higher than those of control group but frequency of sweet snacks intake of HBG was lower than that of control group. There was no difference in daily total energy intake in two groups. Total and supper energy intakes were positively associated with blood glucose. Percent energy intake of alcohol was significantly higher in HBG group and positively related to blood glucose, however there were no difference in daily intake of nutrients in two groups. Alcohol intake was positively related to BMI, but after adjusting BMI, there was no correlation between alcohol intake and blood glucose. Serum total cholesterol and triglyceride were significantly higher in HBG group than those of control group. Serum total cholesterol i,nd triglyceride were positively related to blood glucose and high density lipoprotein cholesterol was negatively associated with blood glucose. After adjusting BMI, serum triglyceride was positively related to blood glucose. In conclusion, weight, BMI, percent body fat and blood total cholesterol, low density lipoprotein cholesterol and triglyceride levels were positively related to blood glucose level of middle aged Korean men exhibiting impaired glucose tolerance. Their eating habits exhibited higher frequency of overeating, fast eating, high energy intakes of supper. (Korean J Nutrition 33(1) : 59-67, 2000)

• Biomolecules & Therapeutics
• /
• 제24권1호
• /
• pp.94-98
• /
• 2016

The objective of the present study was to elucidate the effect of bisphosphonates, anti-osteoporosis agents, on glucose uptake in retinal capillary endothelial cells under normal and high glucose conditions. The change of glucose uptake by pre-treatment of bisphosphonates at the inner blood-retinal barrier (iBRB) was determined by measuring cellular uptake of $[^3H]3$-O-methyl glucose (3-OMG) using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB cells) under normal and high glucose conditions. $[^3H]3$-OMG uptake was inhibited by simultaneous treatment of unlabeled D-glucose and 3-OMG as well as glucose transport inhibitor, cytochalasin B. On the other hand, simultaneous treatment of alendronate or pamidronate had no significant inhibitory effect on $[^3H]3$-OMG uptake by TR-iBRB cells. Under high glucose condition of TR-iBRB cells, $[^3H]3$-OMG uptake was increased at 48 h. However, $[^3H]3$-OMG uptake was decreased significantly by pre-treatment of alendronate or pamidronate compared with the values for normal and high glucose conditions. Moreover, geranylgeraniol (GGOH), a mevalonate pathway intermediate, increased the uptake of $[^3H]3$-OMG reduced by bisphosphonates pre-treatment. But, pre-treatment of histamine did not show significant inhibition of $[^3H]3$-OMG uptake. The glucose uptake may be down regulated by inhibiting the mevalonate pathway with pre-treatment of bisphosphonates in TR-iBRB cells at high glucose condition.