Combined effect of probucol and insulin on renal damage in diabetic rats fed a high cholesterol diet
Eur J Pharmacol. 2006 Oct 24;548(1-3):174-80.
| Combined effect of probucol and insulin on renal damage in diabetic rats fed a high cholesterol diet. |
| Masumi Yoshidaa), Hitoshi Kimuraa), Kouhei Kyukia) and Mikio Itob)a) Pharmacology Division, Nihon Bioresearch Inc.; 6-104 Majima, Fukuju-cho, Hashima, Gifu 501-6251, Japan b) Laboratory of Analytical Pharmacology, Faculty of Pharmacy, Meijo University; 150 Yagotoyama, Tenpaku-ku, Nagoya 468-8503, Japan |
| We investigated the effects of long-term treatment with probucol, a hypolipidemic agent with antioxidative action, insulin, or their combination on renal damage in streptozotocin-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after streptozotocin administration. Daily treatment with probucol, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium, and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals, when histopathological evaluation was performed at 4, 8 and 15 weeks (glomerular and mesangial hypertrophy was observed only at 15 weeks). Combined probucol and insulin treatment was the most effective in suppressing these renal histopathological changes. These results indicate that combined treatment with probucol and insulin is useful in preventing the progression of renal damage in diabetic rats. The possible mechanisms for the preventive effect of this combined treatment will be discussed. |
Increase in the depositon of aggregated protein in the glomeruli of spontaneously diabetic mice
J Pharmacol Sci. 2005 Nov;99(3):287-93.
| Tadashi Nagamatsu1), Yasushi Hirasawa1)2), Yukari Matsui2), Shoko Ohtsu2), Kazusuke Yamane2), Tohru Toyoshi2), Kohei Kyuki2) and Yoshio Suzuki1)1) Department of Pharmacology, Faculty of Pharmacy, Meijo University 2) Nihon Bioresearch Inc. |
| The aim of this study was to investigate the disposal of aggregated protein in the glomeruli of spontaneously diabetic mice. Diabetic mice, KK-A(y) and db/db, and age-matched ICR mice were injected intravenously with aggregated bovine serum albumin (a-BSA) at 0.6 mg/g, and the glomeruli and the blood were obtained. Diabetic mice had larger amounts of a-BSA in their glomeruli than the ICR mice, threefold in KK-A(y) and twofold in db/db, at 3 h after the a-BSA injection. Additionally, the disappearance of a-BSA was retarded in the diabetic glomeruli. KK-A(y) displayed a-BSA in the glomeruli 24 h after the a-BSA injection and db/db did after 12 h, while the ICR did by 8 h. In spite of increases of insulin to similar degrees in both strains of diabetic mice after the a-BSA injection, blood glucose levels markedly decreased in KK-A(y) compared with db/db. There were no histopathological alterations in the glomeruli of the diabetic mice. Depositions of a-BSA were confirmed to be higher in the diabetic glomeruli by the immunofluorescence technique, and KK-A(y) displayed higher depositions of a-BSA than did db/db. The present study suggests that hyperglycemia is involved in the increased deposition of aggregated protein in the glomeruli and that the degradation of aggregated protein is retarded in diabetic glomeruli. |
Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet
Biol Pharm Bull. 2005 Nov;28(11)
| Effect of combined vitamin E and insulin administration on renal damage in diabetic rats fed a high cholesterol diet. |
| Masumi Yoshida1), Hitoshi Kimura1), Kouhei Kyuki1) and Mikio Ito2)1) Pharmacology Division, Nihon Bioresearch Inc. 2) Laboratory of Analytical Pharmacology, Faculty of Pharmacy, Meijo University |
| In the present study, we investigated the effects of a long-term treatment with vitamin E, an antioxidant vitamin, insulin, or their combination on renal damage in streptozotocin (STZ)-induced diabetic rats fed a high cholesterol diet. Increases in urinary albumin and lipid peroxide (LPO) excretions were observed in these diabetic rats, when both urinary parameters were measured at 8 and 15 weeks after STZ administration. Daily treatment with vitamin E, insulin, or their combination markedly suppressed the increase in the 24 h urinary albumin and lipid peroxide excretions. Furthermore, glycogen degeneration of distal tubules, fatty degeneration of glomerular endothelium and hypertrophy of glomeruli and mesangium were observed in the kidneys of the diabetic animals when histopathological evaluation was performed at 4, 8, and 15 weeks (glomerular and mesangial hypertrophy were observed only at 15 weeks). Combined vitamin E and insulin treatment was the most effective at suppressing these renal histopathological changes. These results indicate that combined vitamin E and insulin treatment additively prevents the development and progression of renal damage in diabetic rats. Possible mechanisms for the preventive effect of this combined treatment are discussed. |
Effect of 5-Campestenone (24-methylcholest-5-en-3-one) on Zucker diabetic fatty rats as a type 2 diabetes mellitus model
Horm Metab Res. 2005 Feb;37(2)
| Effect of 5-Campestenone (24-methylcholest-5-en-3-one) on Zucker diabetic fatty rats as a type 2 diabetes mellitus model. |
| Konno R, Kaneko Y, Suzuki K, Matsui Y.Technoflora Co. and Synthetic Organic Chemistry Laboratory, RIKEN, Wako-shi, Saitama, 351-0198, Japan. a Pharmacology Division, Nihon Bioresearch Inc.; 6-104 Mazima, Hukuju-cho, Hashima, Gifu 501-6251, Japan |
| We examined the therapeutic effects of dietary exposure to 5-campestenone (24-methylcholest-5-en-3-one), an enone derivative of campesterol, in Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes mellitus. Dietary 0.6 % exposure to 5-campestenone caused marked reduction in hemoglobin A1c (HbA1c), plasma total cholesterol, triglycerides and non esterified fatty acid (NEFA). In particular, plasma triglyceride levels were reduced in the 0.6 % 5-campestenone-fed group to about 25 % of that in the control group. In the oral glucose tolerance test (OGTT) at three and seven weeks after the beginning of treatment, 5-campestenone limited the rise of blood glucose levels by oral administration of glucose dose-dependently. Amounts of adipose tissue in the retroperitoneum and periepididymal area as well as abdominal subcutaneous fat were significantly decreased in animals fed 0.6 % 5-campestenone. The blood leptin concentration on the final day of feeding was significantly in animals administered 5-campestenone. No obvious anomaly due to consumption of 5-campestenone was detected in necropsy or clinical observations. |
糖尿病モデル動物を用いた糖尿病治療または発症過程における血中glycated albuminの変化
| 糖尿病モデル動物を用いた糖尿病治療または発症過程における血中glycated albuminの変化 Changes in Blood Glycated Albumin in Diabetic Models during the Course of Treatment or Onset of Diabetes |
| 松井 ゆかり，平澤 康史，大津 尚子，長瀬 孝彦，富岡 三和，豊吉 亨，久木 浩平 Yukari Matsui, Yasushi Hirasawa, Shoko Ohtsu, Takahiko Nagase, Miwa Tomioka, Thoru Toyoshi and Kohei Kyuki株式会社日本バイオリサーチセンター 岐阜県羽島市福寿町間島6丁目104番地（〒501-6251） Nihon Bioresearch Inc., 6-104 Majima, Fukuju-cho, Hashima, Gifu 501-6251, Japan, |
| KK-Ay mice, genetically diabetic animal models of type Ⅱ diabetes mellitus, were given feed containing Vogliobose, an α glucosidase inhibitor, for 2 or 4 weeks. And changes in blood glucose, in glycated albumin (abbreviated as “GA” hereafter), and in hemoglobin A1c (abbreviated as “HbAlc” hereafter) were compared. Also changes in these parameters during the course of the onset of diabetes were also compared in rat models for streptozotocin (abbreviated as “STZ” hereafter)-induced diabetes. Feed containing of 0.001% Vogliobose significantly lowered both blood glucose and GA in the KK-Ay mice by the 2- and 4-week feeding. And the Vogliobose containing feed also significantly lowered HbAlc by the 4-week feeding. Feed containing of 0.005% Vogliobose significantly lowered blood glucose, GA, and HbAlc by the 2-week feeding. There was a high correlation between the changes in GA and those in blood glucose (r = 0.8873). Also there was a high correlation between changes in HbAlc and those in blood glucose (r = 0.8720). During the course of onset of STZ-induced diabetes, GA and blood glucose significantly rose the day after administration of STZ compared with the non-treated group; significant differences were seen in the increase of these parameters earlier than HbAlc. The correlation coefficient between the changes in GA and those in blood glucose (r = 0.9361) was higher than that between changes in HbAlc and those in blood glucose (r = 0.7087). Since the changes in GA were noted correspondingly with the falls or rises of blood glucose. And the changes in GA corresponding to those in blood glucose occurred earlier than those in HbAlc. These results suggest that GA serves as a useful item of measurement to assess diabetic morbidity especially after the start of treatment with anti-diabetic drugs or onset of diabetes. |