• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.361-369
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• 2020

Tofacitinib, a Janus kinase inhibitor, was developed for the treatment of rheumatoid arthritis. Recently, it has been associated with an increased change in arthritis development in patients with diabetes. Herein, we evaluated the pharmacokinetics of tofacitinib after intravenous (10 mg/kg) and oral (20 mg/kg) administration to rats with streptozotocin-induced diabetes mellitus and control rats. Following intravenous administration of tofacitinib to rats with streptozotocin-induced diabetes mellitus, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was significantly smaller (33.6%) than that of control rats. This might be due to the faster hepatic intrinsic clearance (112%) caused by an increase in the hepatic cytochrome P450 (CYP) 3A1(23) and the faster hepatic blood flow rate in rats with streptozotocin-induced diabetes mellitus than in control rats. Following oral administration, area under the plasma concentration-time curve from time zero to infinity of tofacitinib was also significantly smaller (55.5%) in rats with streptozotocin-induced diabetes mellitus than that in control rats. This might be due to decreased absorption caused by the higher expression of P-glycoprotein and the faster intestinal metabolism caused by the higher expression of intestinal CYP3A1(23), which resulted in the decreased bioavailability of tofacitinib (33.0%) in rats with streptozotocin-induced diabetes mellitus. In summary, our findings indicate that diabetes mellitus affects the absorption and metabolism of tofacitinib, causing faster metabolism and decreased intestinal absorption in rats with streptozotocin-induced diabetes mellitus.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.51-65
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• 2007

Objective : The present study was carried out to investigate the preventive effect of Sophorae Flos on streptozotocin - induced Diabetes mellitus. Method : Sophorae Flos was given to rats with oral administration. The experimental animals were divided into 3groups : normal group of rats, control group of Streptozotocin-induced diabetic rats, sample group with Sophorae Flos . The effect of Sophorae Flos on Streptozotocin-induced diabetes was observed by measuring the survival rate of rats, weight of rats, FER, blood glucose, each organ weight of rat, total cholesterol, HDL, GOT, GPT & creatinine. Result : Streptozotocin caused hyperglycemia and hypoinsulinemia by a selectively destroying pancreatic ${\beta}-cell$. Sophorae Flos treatment don't protected them from hyperglycemia and hypoinsulinemia. Organ weight liver, kidney, heart & spleen shows no significant changes. Sophorae Flos significantly don't recoverd the increase of several biochemical parameters such as blood glucose, total cholesterol, HDL, GOT, GPT, antioxidant & creatinine is vice versa. Conclusion : Sophorae Flos extract group did not show significant decrease than Streptozotocin control group.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.544-559
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• 2007

Objectives : This study was designed to evaluate the anti-diabetes and vasoelasticity effects of Mori Folium and Aurantii Fructus in streptozotocin-induced type II diabetes mellitus model. Methods : The anti-diabetic effect of Mori Folium and Aurantii Fructus on rats induced with diabetes by streptozotocin was investigated through analyses of changes in body weight, blood glucose, urine volume of rats, viability of human umbilical vein endothelial cells(HUVECs), and elasticity of descending thoracic aorta in rats. The subjects in this study were divided into four groups(n=15): a normal group without any treatment (Con), a normal group with Mori Folium and Aurantii Fructus treatment(Con+P), a diabetes group induced by streptozotocin(STZ), and a Mori Folium and Aurantii Fructus treatment group under diabetes induced by streptozotocin(STZ+P). Rats were administered streptozotocin to induce diabetes. Results : The study showed that Mori Folium and Aurantii Fructus significantly reduced highly increased blood glucose levels(p<0.01) and prevented the diabetic rats from weight loss(p<0.01) and polyurea(p<0.05), Mori Folium and Aurantii Fructus also recovered decreased viability of HUVECs(p<0.01) and damaged elasticity of aorta induced by the streptozotocin (p<0.01). Conclusions: It was concluded from the results that Mori Folium and Aurantii Fructus have a distinct anti-diabetes effect and they also prevent damage of blood vessel induced by diabetes. resulting in prevention of cardiovascular diseases ascribed to diabetes.

• Journal of Pharmacopuncture
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• v.3 no.2
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• pp.99-130
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• 2000

This study was carried out to investigate the effects of Liriopis Tuber Herbal-Acupuncture on Diabetes Mellitus induced by streptozotocin in rat. Body weight, serum insulin, glucose, triglyceride, HDL cholesterol, free cholesterol and total protein were measured in streptozotocin induced diabetic rat injected with Liriopis Tuber Herbal-Acupuncture solution at Pisu(BL20) respectively for 30 days. In order to study the effects of Liriopis Tuber Herbal-Acupuncture at Pisu(BL20) on Diabetes Mellitus induced by Streptozotocin in rat, The groups were divided into five groups; Normal group(non treated group), N.-Saline group(administration of injection with normal saline at BL20 in 30 days after streptozotocin injection), Control group(non treated group after streptozotocin injection), H. Acup. group (administration of Liriopis Tuber Herbal-Acupuncture at BL20 in 30 days after streptozotocin injection), and Acup. group (administration of acupuncture at BL20 in 30 days after streptozotocin injection). The results obtained were summarized as follows; 1. As compared with Control group, there wae no significant tendency to diminish the rate of weight loss in H. - Acup. group. 2. As compared with Control group, there wae signiticant increase of serum insulin level in H. -Acup. group. 3. As compared with Control group, there was decrease of glucose level in H.- Acup. group. 4. As compared with Control group, there was decrease of triglyceride level in H. - Acup. group. 5. As compared with Control group, trere wae increase of HDL cholesterol level in H. - Acup. group. 6. As compared with Control group, there was significant increase of free cholesterol level in H. - Acup. group. 7. As compared with Control group, there was Increase of total protein level in H. - Acup. group. According to above mentioned results, Liriopis Tuber Herbal-Acupuncture was expected to be effective in treatment of Diabetes Mellitus and its complications.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.20 no.1 s.32
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• pp.154-168
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• 2007

Objective : The present study was carried out to investigate the preventive effect of Agrimonia pilosa Ledebour on Streptozotocin(STZ)-induced Diabetes mellitus. Method : Agrimonia pilosa Ledebour was given to rats with oral administration. The experimental animals were divided into 3groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with Agrimonia pilosa Ledebour. The effect of Agrimonia pilosa Ledebour on STZ-induced diabetes was observed by measuring the survival rate of rats, weight of rats, FER, blood glucose, each organ weight of rat, total cholesterol, HDL, GOT, GPT & creatinine. Result : STZ caused hyperglycemia and hypoinsulinemia by a selectively destroying pancreatic ${\beta}-cell$. Agrimonia pilosa Ledebour treatment don't protected them from hyperglycemia and hypoinsulinemia. Organ weight only liver weight decreased but kidney, heart & spleen shows no significant changes. Agrimonia pilosa Ledebour significantly don't recoverd the increase of several biochemical parameters such as blood glucose, total cholesterol, HDL, GOT, GPT & creatinine is vice versa. Conclusion : Agrimonia pilosa Ledebour extract group did not show significant difference compared with STZ-induced Diabetes Mellitus group.

• The Korea Journal of Herbology
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• v.23 no.3
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• pp.175-180
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• 2008

Objecitivies : While Glechoma longituba (Nakai) Kupr(GL) has been known as a antiinflammatory, antidiabetic and antihypertension medicine in korea traditional medicine, there has been only a few researches about it in Korea. Thus, we examined antidiabetic effect of GL in diabetic rats induced by streptozotocin Methods : To verify the effects of GL on serum glucose, creatinine, BUN, total cholesterol and triglyceride through streptozotocin-induced diabetic rats, some rats were injected 1 time with 55mg/kg streptozotocin intraperitoneally to induce diabetes, and other rats were injected with buffer I.P. as control group. Results : GL extracts significantly reduced the amount of serum glucose, BUN, creatinine, and triglyceride level in diabetics rats induced by streptozotocin. Conclusions : According to above result, Glechoma longituba was expected to be applied to the treatment of diabetes mellitus.

• Journal of Nutrition and Health
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• v.26 no.7
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• pp.851-857
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• 1993

Atherosclerotic vascular disease is a major cause of the increased morbidity and mortality assciated with diabetes mellitus. The prominent role of nutrition in hypercholesteolemia and atherosclerosis is generally accepted. Diet is a key element in the management of diabetes (type I-IDDM), yet the appropriate diet for patient with diabetes mellitus is not well known. Dietary protein has been shown to have a significant effect on plasma cholesterol levels in both experimental animals and humans. The present experiment was designed to determine the effect of the dietary protein level(20% vs 60%) on plasma glucose concentration, lipids profile, insulin and glucagon levels from non-diabetic and streptozotocin-induced diabetic rats. Results showed that a high protein diet decreased triglyceride concentration in diabetic rats. Also diabetic rats fed a high protein diet were hypocholesterolemic than rats fed a control diet. There were no effects by level of protein on fasting blood glucose concentration and insulin/glucagon ratio. Results from the present study suggest that a high protein diet may be beneficial to control pasma lipids in chemically-induced diabetic rats.

• Journal of Acupuncture Research
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• v.25 no.1
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• pp.57-72
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• 2008

Objectives : The Herb-combined Remedy(HCR) for diabetes mellitus is known as an anti-hyperglycaemic agent. But its exact mechanisms are unclear. The present study was carried out to investigate its anti-hyperglycaemic and anti-oxidative effects in STZ-induced diabetic rats. Methods : Experimental diabetes was induced by injection of STZ(80mg/kg) to ratsvia the peritoneum. The experimental animals were divided into 4 groups : normal group, control group(STZ-induced diabetic rats with no treatment), HCR group(STZ-induced diabetic rats with HCR treatment), MF group(STZ-induced diabetic rats with Metformin treatment). The effects of HCR on STZ-induced diabetes was observed by measuring fasting blood glucose, changes of body weight, food uptake, and water uptake glucose levels in the normal state decline rates in blood glucose levels DPPH free-radical scavenging activity superoxide dismutase in RBC lysate catalase activity in RBC lysate and glutathione reductase activity in RBC lysate. Results : Treatment with HCR regulated blood glucose levels. Treatment with HCR also prevented weight loss in STZ-induced diabetic rats. In addition, oral glucose tolerance decreased following treatment with HCR. Direct anti-oxidative effects on DPPH free-radical scavenging were not observed, but treatment with HCR elevated SOD levels in blood cell lysates from STZ-induced diabetic rats. In addition, the HCR-treatment group showed an elevated tendency to glutathione reductase activity. Conclusions : These results demonstrate that HCR has anti-hyperglycaemic and anti-oxidative effects in STZ-induced diabetic rats.

• Journal of Pharmacopuncture
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• v.9 no.1
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• pp.33-44
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• 2006

Objectives : We performed this study in order to investigate the effects of Sedang-hwan(世糖丸) on the diabetes mellitus. Methods : We injected a vein with 65mg/kg of streptozotocin(STZ) on the rats. And then administered Sedang-hwan; 18.7mg/kg/day to sample groups and observed the weight and glucose level, insulin, C-peptide, triglyceride, albumin, T-protein, BUN(Blood Urea Nitrogen) and creatinine in blood. Results : 1. The sample groups showed a high suppressive effect of weight loss(P=0.002). 2. The sample groups' glucose level showed a effective in lowering level(P=0.001). 3. The sample groups showed a higher insulin level than control groups. 4. The sample groups showed a higher C-peptide level than control groups(P=0.001). 5. The sample groups' triglyceride level showed a effective in lowering level. 6. The sample groups showed a higher HDL-cholesterol level than control groups(P<0.001). 7. The sample groups showed a higher T-protein level than control groups(P=0.04). 8. The sample groups showed a higher albumin level than control groups(P<0.001). 9. The sample groups' creatinine level showed a effective in lowering level(P=0.04). 10. The sample groups' BUN level showed a effective in lowering level(P=0.03). Conclusions : Conclusively, Sedang-hwan was recognized to have decrease effect of serum glucose, triglyceride, creatinine, BUN of the diabetic rats induced by streptozotocin. It was suggested that Sedang-hwan can be used for effective diabetes mellitus medical treatment. It is also required to study further about detailed principles of blood-sugar dropping effect by Sedang-hwan, and recovery by diabetes mellitus.

• Archives of Pharmacal Research
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• v.26 no.7
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• pp.559-563
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• 2003

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of $\beta$-cell destruction in insulin-dependent diabetes mellitus. In non insulin-dependent diabetes, cytokines are also associated with impaired $\beta$-cell function in high glucose condition. By the screening of various natural products blocking $\beta$-cell destruction, we have recently found that epigallocatechin gallate (EGCG) can prevent the in vitro destruction of RINm5F cell, an insulinoma cell line, that is induced by cytokines. In that study we suggested that EGCG could prevent cytokine-induced $\beta$-cell destruction by down-regulation of nitric oxide synthase (NOS) through inhibition of NF-kB activation. Here, to verify the in vivo antidiabetogenic effect of EGCG, we examined the possibility that EGCG could also prevent the experimental autoimmune diabetes induced by the treatment of multiple low doses of streptozotocin (MLD-STZ), which is recognized as an inducer of type I autoimmune diabetes. Administration of EGCG (100 mg/day/kg for 10 days) during the MLD-STZ induction of diabetes reduced the increase of blood glucose levels caused by MLD-STZ. Ex vivo analysis of $\beta$-islets showed that EGCG downregulates the MLD-STZ-induced expression of inducible NOS (iNOS). In addition, morphological examination showed that EGCG treatment ameliorated the decrease of islet mass induced by MLD-STZ. In combination these results suggest that EGCG could prevent the onset of MLD-STZ-induced diabetes by protecting pancreatic islets. Our results therefore revealed the possible therapeutic value of EGCG for the prevention of diabetes mellitus progression.