• Natural Product Sciences
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• v.29 no.2
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• pp.91-97
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• 2023

Mangosteen peel extract is a xanthone group, that plays an important role in anti-angiogenesis. This study investigated mangosteen peel extract on cerebral neovascularization in type 2 diabetes mellitus (DM) rats. This study used 36 rats, randomized into six groups: C1 (negative control); C2 (high fat diet (HFD) and mangosteen peel extract at 200 mg/kg BW); C3 (HFD and diabetic); E1, E2, and E3 (HFD, diabetic, and extract at 100, 200, and 400 mg/kg BW respectively). All groups were measured body mass index (BMI), homeostasis model assessment-insulin resistance (HOMA-IR) and β cell function (HOMA-B), and histopathological feature of cerebral vascular (CV). There were significant differences in BMI, HOMA-IR, HOMA-B, and the mean number of CV (all p < 0.05) among treatment groups. E1-3 groups had a significantly lower level of blood glucose and HOMA-IR, and a higher level of HOMA-B and BMI (all p < 0.05) which tends to reduce cerebral neovascularization. HOMA-IR independently had a positive effect to induce neovascularization of CV (p < 0.05, R² = 26.8%). These findings suggested that mangosteen peel extract increased β-cell function sensitivity, and effectively suppressed insulin resistance, BMI, and cerebral neovascularization process in type 2 DM rats.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.6
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• pp.581-593
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• 2016

The advantages of monounsaturated fatty acids (MUFAs) on insulin resistance and type 2 diabetes mellitus (T2DM) have been well established. However, the molecular mechanisms of the anti-diabetic action of MUFAs remain unclear. This study examined the anti-hyperglycemic effect and explored the molecular mechanisms involved in the actions of fish oil- rich in MUFAs that had been acquired from hybrid catfish (Pangasius larnaudii${\times}$Pangasianodon hypophthalmus) among experimental type 2 diabetic rats. Diabetic rats that were fed with fish oil (500 and 1,000 mg/kg BW) for 12 weeks significantly reduced the fasting plasma glucose levels without increasing the plasma insulin levels. The diminishing levels of plasma lipids and the muscle triglyceride accumulation as well as the plasma leptin levels were identified in T2DM rats, which had been administrated with fish oil. Notably, the plasma adiponectin levels increased among these rats. The fish oil supplementation also improved glucose tolerance, insulin sensitivity and pancreatic histological changes. Moreover, the supplementation of fish oil improved insulin signaling ($p-Akt^{Ser473}$ and p-PKC-${\zeta}/{\lambda}^{Thr410/403}$), $p-AMPK^{Thr172}$ and membrane GLUT4 protein expressions, whereas the protein expressions of pro-inflammatory cytokines (TNF-${\alpha}$ and nuclear NF-${\kappa}B$) as well as p-PKC-${\theta}^{Thr538}$ were down regulated in the skeletal muscle. These data indicate that the effects of fish oil-rich in MUFAs in these T2DM rats were partly due to the attenuation of insulin resistance and an improvement in the adipokine imbalance. The mechanisms of the anti-hyperglycemic effect are involved in the improvement of insulin signaling, AMPK activation, GLUT4 translocation and suppression of pro-inflammatory cytokine protein expressions.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.2
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• pp.196-201
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• 2013

Abnormal regulation of glucose and impaired lipid metabolism that result from a defective or deficient insulin are the key etiological factor in type 2 diabetes mellitus (T2DM). The our study evaluated the beneficial effect of diet supplementation with Lentinus edodes on hyperglycemia and lipid metabolism in normal and type 2 diabetic rats. The animals were divided into 4 groups: group I(control) rats were fed standard diet (12% of calories as fat); group II (T2DM) rats were fed HFD (40% of calories as fat) for 2 weeks and then injected with STZ (50 mg/kg); group III and group IV rats were continually fed a diet containing 1% and 10% Lentinus edodes for 4 weeks after T2DM induction, respectively. After 4 weeks we determined biochemical parameters such as glucose, insulin concentration, serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), and glycosylated hemoglobin (HbA1c) concentration were also measured. There was a significant reduction in serum TC and TG in the Lentinus edodes supplement groups. The Lentinus edodes diet supplementation were found to have a potent lipid metabolism improvement as well as LDL concentration decreased and HDL concentration was increased. Concentrations of blood glucose and HbA1c in the experimental groups II were significantly decreased after 4 weeks compared with the control group. The Lentinus edodes diet supplementation is useful in regulating the glucose level, improves the insulin, HbA1c, serum lipid metabolism in experimental diabetic rats. We suggest that Lentinus edodes supplementation may have the control effects of diabetes mellitus by improving blood glucose control and lipid metabolism.

• The Korean Journal of Physiology and Pharmacology
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• v.28 no.1
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• pp.1-10
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• 2024

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and dyslipidemia. Carvacrol (CAR) has demonstrated the potential to mitigate dyslipidemia. This study aims to investigate whether CAR can modulate blood glucose and lipid levels in a T2DM rat model by regulating short-chain fatty acids (SCFAs) and the GPR41/43 pathway. The T2DM rat model was induced by a high-fat diet combined with low-dose streptozocin injection and treated with oral CAR and/or mixed antibiotics. Fasting blood glucose, oral glucose tolerance, and insulin tolerance tests were assessed. Serum lipid parameters, hepatic and renal function indicators, tissue morphology, and SCFAs were measured. In vitro, high glucose (HG)-induced IEC-6 cells were treated with CAR, and optimal CAR concentration was determined. HG-induced IEC-6 cells were treated with SCFAs or/and GPR41/43 agonists. CAR significantly reduced blood lipid and glucose levels, improved tissue damage, and increased SCFA levels in feces and GPR41/43 expression in colonic tissues of T2DM rats. CAR also attenuated HG-induced apoptosis of IEC-6 cells and enhanced GPR41/43 expression. Overall, these findings suggest that CAR alleviates blood lipid and glucose abnormalities in T2DM rats by modulating SCFAs and the GPR41/43 pathway.

• Nutrition Research and Practice
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• v.18 no.5
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• pp.633-646
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• 2024

BACKGROUND/OBJECTIVES: Cladophora glomerata extract (CGE), rich in polyphenols, was reported to exhibit antidiabetic and renoprotective effects by modulating the functions of protein kinases-mediated organic anion transporter 1 (Oat1) and 3 (Oat3) in rats with type 2 diabetes mellitus (T2DM). Nevertheless, the antioxidant effects of CGE on such renoprotection have not been investigated. This study examined the mechanisms involved in the antioxidant effects of CGE on renal organic anion transport function in an in vivo study. MATERIALS/METHODS: Diabetes was induced in the rats through a high-fat diet combined with a single dose of 40 mg/kg body weight (BW) streptozotocin. Subsequently, normal-diet rats were supplemented with a vehicle or 1,000 mg/kg BW of CGE, while T2DM rats were supplemented with a vehicle, CGE, or 200 mg/kg BW of vitamin C for 12 weeks. The study evaluated the general characteristics of T2DM and renal oxidative stress markers. The renal organic transport function was assessed by measuring the para-aminohippurate (PAH) uptake using renal cortical slices and renal inflammatory cytokine expression in the normal diet (ND) and ND + CGE treated groups. RESULTS: CGE supplementation significantly reduced hyperglycemia, hypertriglyceridemia, insulin resistance, and renal lipid peroxidation in T2DM rats. This was accompanied by the normalization of high expressions of renal glutathione peroxidase and nuclear factor kappa B by CGE and vitamin C. The renal anti-inflammation of CGE was evidenced by the reduction of tumor necrosis factor-1α and interleukin-1β. CGE directly blunted sodium nitroprusside-induced renal oxidative/nitrosative stresses and mediated the PAH uptake in the normally treated CGE in rats was particularly noteworthy. These data also correlated with reduced nitric oxide production, highlighting the potential of CGE as a therapeutic agent for managing T2DM-related renal complications. CONCLUSION: These findings suggest that CGE has antidiabetic effects and directly prevents diabetic nephropathy through oxidative/nitrosative stress pathways.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.4
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• pp.341-354
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• 2021

Cardamonin (CARD) is a chalconoid with anti-inflammatory and antioxidant properties, and it is present in several plants. We sought to explore whether CARD exerts any positive effects against hyperglycemia-induced testicular dysfunction caused by type 2 diabetes and aimed to identify its possible intracellular pathways. Adult male rats were subdivided into six groups: control, CARD, diabetic (DM), DM + glibenclamide (GLIB), DM + CARD and DM + GLIB + CARD. Type 2 DM induced a significant increase in blood glucose and insulin resistance, along with diminished serum insulin, testosterone and gonadotropins levels, which were associated with the impairment of key testicular androgenic enzymes and cellular redox balance. Administration of CARD at a dose of 80 mg/kg for 4 weeks effectively normalized all of these alterations, and the improvement was confirmed by epididymal sperm analysis. After treatment with CARD, the pathological changes in spermatogenic tubules were markedly improved. Significantly, CARD upregulated testicular glucose transporter-8 (GLUT-8) expression and had inhibitory effects on elevated autophagy markers and caspase-3 immunoreactive cells. Furthermore, our results revealed that CARD was able to attenuate damage via activation of Nrf2 through the p62-dependent degradation of testicular anti-Kelch-like ECH-associated protein-1 (Keap-1). In conclusion, this study suggests that CARD provides protection against diabetic stress-mediated testicular damage. The use of CARD with conventional anti-diabetic therapy was associated with improved efficacy compared with conventional therapy alone.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.2
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• pp.167-173
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• 2016

This study investigated the effects of green tea polyphenol and vitamin C on type 2 diabetes mellitus by administering polyphenon 60 (P60) and sodium ascorbate (SA) to diabetic rats induced by high fat diet/low-dose streptozotocin. The experimental group was divided into five different groups: non-diabetic control group (NC), diabetes control group (DC), diabetes+P60 group (DM+P60), diabetes+SA group (DM+SA), and diabetes+P60+SA group (DM+P60+SA). P60 and SA were dissolved in 0.1% drinking water. After P60 and SA were administered for 16 weeks, fasting blood glucose, plasma insulin, serum triglyceride, blood urea nitrogen (BUN), and creatinine levels as well as kidney alkaline phosphatase (AP) and ${\gamma}$-glutamyltranspeptidase (GGT) activities were measured. Fasting blood glucose level increased 5-fold in the DC group compared to the NC group. In the DM+P60 group, fasting blood glucose level decreased by 14%. In the DM+P60+SA group, fasting blood glucose level decreased by 28% compared to the DC group, whereas the DM+SA group did not show any significant difference. The homeostasis model assessment for insulin resistance index increased in the DC group and decreased in the DM+P60+SA group compared to the DC group. Serum creatinine level increased in the DC group, but decreased by 17% in the DM+P60 group and by 43% in the DM+P60+SA group compared to the DC group. The serum BUN level increased in the DC group, but decreased by 41% in the DM+P60+SA group compared to the DC group. Kidney GGT and AP activities decreased in the DC group compared to the NC group; however, they were reversed by DM+P60+SA group. These results show that combined administration of both green tea polyphenol and vitamin C had better effects on improving blood glucose level, insulin resistance, serum triglyceride level, and protecting kidneys than administration of either green tea polyphenol or vitamin C alone in the context of type 2 diabetes.

• The Journal of Internal Korean Medicine
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• v.38 no.1
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• pp.10-19
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• 2017

Objective: This study reviewed experimental studies on the effects of Korean medical treatment for diabetes mellitus (DM). Method: We reviewed 24 studies about DM that had been published since 2013. We searched the Korean Institute of Oriental Medicine (KIOM) database with the keyword '당뇨', '消渴', 'Diabetes'. Results: 1. The studies used various Korean medicine treatments; 15 used single medicinal herbs, 6 used herbal complexes, and 2 used acupuncture. 2. The measurement parameters used in the studies included blood glucose, body weight, histochemical change, lipid parameters, and food/water intake. Anti-diabetic effects were demonstrated in most of the studies. 3. The experimental animals used were rats or mice. There were 15 type 1 diabetes models, 7 type 2 diabetes models, and one normal model. Among them, 13 cases of chemical diabetes induced by Streptozotosin (STZ, type 1 diabetes inducer) were the most common. Conclusion: Further articles on Korean medical treatment of DM should be studied.

• The Korean Journal of Physiology and Pharmacology
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• v.14 no.2
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• pp.99-103
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• 2010

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous type 2 diabetes (T2D), develops hyperglycemic obesity with hyperinsulinemia and insulin resistance after the age of 25 weeks, similar to patients with noninsulin-dependent diabetes mellitus (DM). In the present study, we determined whether there are differences in the pattern of gene expression related to glucose and lipid metabolism between OLETF rats and their control counterparts, Long-Evans Tokushima (LETO) rats. The experiment was done using 35-week-old OLETF and LETO rats. At week 35 male OLETF rats showed overt T2D and increases in blood glucose, plasma insulin, plasma triglycerides (TG) and plasma total cholesterol (TC). Livers of diabetic OLETF and LETO rats also showed differences in expression of mRNA for glucose and lipid metabolism related genes. Among glucose metabolism related genes, GAPDH mRNA was significantly higher and FBPase and G6Pase mRNA were significantly lower in OLETF rats. For lipid metabolism related genes, HMGCR, SCD1 and HL mRNA were substantially higher in OLETF rats. These results indicate that gluconeogenesis in OLETF rats is lower and glycolysis is higher, which means that glucose metabolism might be compensated for by a lowering of the blood glucose level. However, lipid synthesis is increased in OLETF rats so diabetes may be aggravated. These differences between OLETF and LETO rats suggest mechanisms that could be targeted during the development of therapeutic agents for diabetes.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.493-501
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• 2018

The present study was carried out with the hypothesis that combination of canagliflozin and omega-3 fatty acid may have potential effect on insulin level, insulin resistance, cardiac biomarkers, inflammatory cytokines and histological studies in type 2 diabetes mellitus (DM). Type 2 DM was induced by injecting nicotinamide (120 mg/kg, i.p.) 15 min before STZ (60 mg/kg) injection. Canagliflozin (5 and 10 mg/kg) and omega-3 fatty acid (300 mg/kg) were given for 28 days after confirmation of diabetes. Biochemical estimations revealed elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines in diabetic group. Daily dosing of alone canagliflozin and omega-3 fatty acid slightly reduced elevated levels of glucose, insulin, HOMA-R and inflammatory cytokines ($IL-1{\beta}$, IL-2, and $TNF{\alpha}$), whereas canagliflozin and omega-3 fatty acid combination has reduced these biochemical parameters significantly when compared with diabetic group. Similarly in diabetic group the levels of cardiac biomarkers such as lipid profile, LDH, CKMB and troponin were significantly increased. Elevated levels of cardiac biomarkers were significantly reduced after daily dosing of alone canagliflozin and omega-3 fatty acid. Canagliflozin and omega-3 fatty acid combination has offered better improvement in cardiac biomarkers compared to alone canagliflozin and omega-3 fatty acid. Histopathological analysis also supported the above hypothesis that combination therapy (canagliflozin and omega-3 fatty acid) offered better protection against degenerative changes in ${\beta}-cells$ of pancreas as compared to alone treatment with these drugs. Thus the present study revealed that canagliflozin and omega-3 fatty acid can be used as potential combination therapy in type 2 DM along with cardiac complication.