저강도 treadmill 운동이 streptozotocin 유도 당뇨쥐의 혈당, 인슐린 및 지질 농도에 미치는 영향

김세종,서혜림,고정림,염종우,예정복,이선주,김경환,손원협,장은숙 한국생명과학회 2004 생명과학회지 Vol.14 No.2

본 연구는 streptozotocin으로 당뇨병을 유도하는 조건들을 농도에 따른 변화를 관찰하고, 적절한 조건에서 당뇨쥐에서의 저강도의 treadmill 운동이 체중과 혈중의 당, 인슐린 및 지질의 변화에 미치는 영향을 알아보고자 실시하였으며, 연구결과를 요약하면 다음과 같다. 실험 I에서 STZ 주사량이 40 mg/mg으로 높아질수록 정상군에 비해 혈당이 유의하게 증가하고, 반대로 체중과 인슐린 농도는 상대적으로 감소하였다. 실험II에서 STZ 주사를 한 모든 군에서 혈당이 유의하게 증가하지만 BE군은 C군에 비해 그 증가율이 유의하게 억제되었으며, 운동이 인슐린 농도와 혈중지질 농도를 정상적으로 유도하는 것으로 나타났다. 특히, 당뇨 유발 전부터 운동을 실시한 경우 그 효과가 더욱 유의하게 나타났으며, 앞으로 당뇨 유발의 정도와 운동 빈도 및 강도와 관련된 더욱 많은 연구가 이루어져야 할 것으로 사료된다. Exercise is beneficial to the diabetic patients and streptozotocin-induced diabetic rat has been used for the study of exercise effect. The purpose of this study was to establish the optimal condition of induction of hyperglycemic diabetic rat using streptozotocin and to examine the preventive effect of treadmill exercise on the diabetic rat before and after streptozotocin injection. Intraperitoneal injection of increasing amount of streptozotocin up to 40 mg/kg dose-responsively induce hyperglycemic diabetic rat and inversely reduced the blood insulin level. Body weight was also gradually reduced with the increasing amount of streptozotocin. Control and diabetic rats exercised for 4 weeks before streptozotocin injection. The exercise was performed in the treadmill for 25 minutes a day and 5 times a week with low intensity (0 degree tilt, 15 m/min velocity). Following streptozotocin injection, the blood glucose level was measured every week and the rat was sacrificed after 4 weeks to measure the concentration of insulin and blood lipids. The blood levels of glucose and insulin was significantly reduced with exercise before streptozotocin injection, while those were not changed after streptozotocin injection. The levels of blood lipids such as total cholesterol, HDL-cholesterol, LDL-cholesterol and triglyceride were close to normal control rats. From this study, researchers found the optimal condition of preparation of streptozotocin-induced hyperglycemic diabetic rat, and the mild treadmill exercise has beneficial effect on preventing hyperglycemia and hyperlipidemia. Thus, even low intensive running prevent not only diabetes but also diabetic vascular complications.

Effects of Diabetes Mellitus on the Disposition of Tofacitinib, a Janus Kinase Inhibitor, in Rats

( Eun Hye Gwak ),( Hee Young Yoo ),( So Hee Kim ) 한국응용약물학회 2020 Biomolecules & Therapeutics(구 응용약물학회지) Vol.28 No.4

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.

Impaired Endothelium-Dependent Relaxation is Mediated by Reduced Production of Nitric Oxide in the Streptozotocin-Induced Diabetic Rats

Kyoung Sook Park,Cuk Seong Kim,Sang Won Kang,Jin Bong Park,Kwang-Jin Kim,Seok Jong Chang,Byeong Hwa Jeon 대한생리학회-대한약리학회 2000 The Korean Journal of Physiology & Pharmacology Vol.4 No.3

<P> To evaluate the involvement of nitric oxide production on the endothelium-dependent relaxation in diabetes, we have measured vascular and endothelial function and nitric oxide concentration, and the expression level of endothelial nitric oxide synthase in the streptozotocin-induced diabetic rats. Diabetic rats were induced by the injection of streptozotocin (50 mg/kg i.v.) in the Sprague-Dawley rats. Vasoconstrictor responses to norepinephrine (NE) showed that maximal contraction to norepinephrine (10<SUP>⁣5 </SUP>M) was significantly enhanced in the aorta of diabetic rats. Endothelium-dependent relaxation induced by acetylcholine was markedly impaired in the aorta of diabetic rats, these responses were little improved by the pretreatment with indomethacin. However, endothelium-independent relaxation induced by nitroprusside was not altered in the diabetic rats. Plasma nitrite and nitrate (NO<SUB>2</SUB>/<SUB>3</SUB>) levels in diabetic rats were significantly lower than in non-diabetic rats. Western blot analysis using a monoclonal antibody against endothelial cell nitric oxide synthase (eNOS) revealed that the protein level was lower in the aorta of diabetic rats than in non-diabetic rats. These data indicate that nitric oxide formation and eNOS expression is reduced in diabetes, and this would, in part, account for the impaired endothelium-dependent relaxation in the aorta of streptozotocin-induced diabetic rats.

Streptozotocin 유도 당뇨 Rat에 한약제제의 급여가 혈당 및 지질 농도에 미치는 영향

卞富亨,徐富一 대한본초학회 2004 大韓本草學會誌 Vol.19 No.1

Objectives: To examine the effect of Oriental herb medicines on serum glucose and lipid concentration in streptozotocin-induced diabetic rats. For this study, the materials concerned with the useful Oriental herb medicines for Diabetes MellitudDM) were collected at the clinic of Daegu Haany University. Methods: To verify the effects of Oriental herb medicines on serum glucose through streptozotocin-induced diabetic rats, some rats were injected 1 time with 50 mghg streptombcin intraperitoneally(1.P.) to induce diabetes, and other rats were injected with buffer I.P. as control group. Results: The concentration of serum glucose in SZ(streptozotocin) plus Oriental herb medicines extract group was significant decrease than SZ(streptozotocin) control group(p<0.05). The concentration of cholesterol in SZ(streptozotocin) plus Oriental herb medicines extract group did not shown significant decrease than SZ(streptozotocin) control group(p<0.05). Also the concentration of triglycende in SZ(streptozotocin) plus Oriental herb medicines extract group did not shown significant decrease than SZ(streptozotocin) control group(p<0.05). Conclusion: These results suggest that Oriental herb medicines extract used in this experimental could be applied to the treatment of diabetes mellitus.

糖尿1號方의 藥鍼 및 口腔投與가 Streptozotocin에 의한 흰쥐의 糖尿病性 腎症에 미치는 영향

나건호,조명래,조수인 대한침구의학회 2005 대한침구의학회지 Vol.20 No.6

Objective : The present study was carried out to investigate the preventive effect of Anti-diabetic prescription 1(AD-1) on streptozotocin(STZ)-induced diabetic nephropathy. Methods : AD-1 consists of eleven herbs that have an effect on diabetes mellitus. AD-1 was given to rats with the combination of oral administration and herbal-acupuncture stimulation. The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with AD-1 treatment. Experimental diabetes was induced by the injection of STZ(60㎎/㎏) to the rat via the peritoneum. The effect of AD-1 on STZ-induced diabetic nephropathy was observed by measuring the serum level of creatinine and BUN. Urine secretion of albumin for 24 hours and urine level of glucose measures too. Anti-oxidative stress of AD-1 administration in living body was estimated by measuring lipid peroxide and GSH content in cortex of kidneys. Results : STZ induced increase of serum creatinine, BUN and albumin secretion were lowered by AD-1 treatment. Conclusions : The AD-1 treatment showed protective effect on rat diabetic nephropathy model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.

당뇨1호방의 약침 및 구강투여가 Streptozotocin에 의한 흰쥐의 당뇨병성 신증에 미치는 영향

나건호,조수인,조명래 대한침구의학회 2005 대한침구의학회지 Vol.22 No.5

Objectives : The present study was carried out to investigate the preventive effect of Anti-diabetic prescription 1(AD-1) on streptozotocin(STZ)-induced diabetic nephropathy. Methods : AD-1 consists of eleven herbs that have an effect on diabetes mellitus. AD-1 was given to rats with the combination of oral administration and herbal-acupuncture stimulation. The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with AD-1 treatment. Experimental diabetes was induced by the injection of STZ(60㎎/㎏) to the rat via the peritoneum. The effect of AD-1 on STZ-induced diabetic nephropathy was observed by measuring the serum level of creatinine and BUN. Urine secretion of albumin for 24 hours and urine level of glucose measures too. Anti-oxidative stress of AD-1 administration in living body was estimated by measuring lipid peroxide and GSH content in cortex of kidneys. Results : STZ induced increase of serum creatinine, BUN and albumin secretion were lowered by AD-1 treatment. Conclusion : The AD-1 treatment showed protective effect on rat diabetic nephropathy model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.

한약복합처방의 경구투여가 Streptozotocin에 의해 유발된 당뇨병 백서의 혈당과 항산화효소계에 미치는 영향

이은방,조명래,김재홍,류충열 대한침구의학회 2008 대한침구의학회지 Vol.25 No.1

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(80㎎/㎏) 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.

韓藥複合處方 藥鍼 및 經口投與가 Streptozotocin에 의한 흰쥐의 糖尿病과 抗酸化能에 미치는 영향

박사현,조수인,채우석,조명래 대한침구의학회 2005 대한침구의학회지 Vol.20 No.6

Objective : The present study was carried out to investigate the preventive effect of Several Herb-combind Prescription(SHP) on Streptozotocin (STZ) -induced Diabetes mellitus. Methods : SHP was given to rats with the combination of oral administration and herbal-acupuncture stimulation. The experimental animals were divided into 3 groups : normal group of rats, control group of STZ-induced diabetic rats, sample group with SHP treatment. In vitro test of SHP showed α-glucosidase inhibition, DPPH radical scavenging activity and inhibition of lipid peroxidation. Experimental diabetes was induced by the injection of STZ(60㎎/㎏) to the rat via the peritoneum. The effect of SHP on STZ-induced diabetes was observed by measuring the serum level of insulin, glucose, triglyceride, total cholesterol and lipid peroxides. Hepatic activities of catalase and reduced glutathione were examined and insulin granule was observed by immunohistochemical examination. Results : STZ caused hyperglycemia and hypoinsulinemia by a selectively destroying pancreatic β-cell. SHP treatment protected them from the hyperglycemia and hypoinsulinemia. STZ induced increase of serum triglyceride lowered by SHP treatment. And by SHP treatment, pancrease showed a big area with positive immuno-reactivity for presence of insulin with many insulin granules distributed in the β-cells in the islets of Langerhans. Conclusions : The SHP treatment showed protective effect on diabetic rat model, and action mechanism of the effect was thought to be concerned with anti-oxidative stress.

한약재 함유 대두발효 추출물이 streptozotocin으로 유발된 당뇨 흰쥐의 혈당 및 조직형태학적 변화에 미치는 영향

조창숙 ( Chang Suk Jo ),김소영 ( So Young Kim ),최문열 ( Moon-yeol Choi ),김미형 ( Mi Hyung Kim ),김미려 ( Mi Ryeo Kim ),서부일 ( Bu-il Seo ) 대한본초학회 2022 大韓本草學會誌 Vol.37 No.1

Objective : This study was designed to investigate anti-diabetic effects of fermented soy bean extract with herbal medicines (Godjang) in diabetic rat models induced by streptozotocin (STZ) injection. Method : Changes in body weight, drinking water, and food intake were observed for 4 weeks before and after induction of diabetes mellitus in rats. The anti-diabetic capacity of Godjang was analyzed by fasting blood glucose (FBG) every week. Also, after 4 weeks of administration, the oral glucose tolerance test (OGTT) was performed, and then blood levels of insulin were checked. And serum levels of total cholesterol and triglycerides were determined. Histomorphological changes of liver, kidney and pancreatic tissues were also observed in STZ-induced diabetic rats and Godjang administered rats. Result : In Godjang administered group, body weight and water intake were more lower than that of STZ-induced diabetic rats. FBG was decreased in the Godjang administered group than STZ-induced diabetic group. According to OGTT, blood glucose levels at 30 minutes and 60 minutes significantly decreased in Godjang administered group than in STZ-induced diabetic control group. Administration of Godjang extract for 4W significantly decreased levels of serum glucose, total cholesterol (TC), triglycerides (TG) in diabetic rats. In histomorphological analysis of kidney, liver, Godjang administrated groups showed the inhibition of pathological damage. Conclusion : These results suggest that Godjang extract has an anti-diabetic action through decrease in serum glucose, TC, TG levels and recovery of the morphological changes in kidney and liver in STZ-induced diabetic rats.1)

Epigallocatechin Gallate Prevents Autoimmune Diabetes Induced by Multiple Low Doses of Streptozotocin in Mice

Eun-KyungSong,HyeonHur,Myung-KwanHan 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.7

Cytokines produced by immune cells infiltrating pancreatic islets have been incriminated as important mediators of b-cell destruction in insulin-dependent diabetes mellitus. In non insulindependent diabetes, cytokines are also associated with impaired b-cell function in high glucose condition. By the screening of various natural products blocking b-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 b-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 b-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.