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Animal Bioresource in Japan

.: Home > Animal Bioresource in Japan > 2015 > Volume 64 Number 2 > Yoshiaki Katsuda1), Tomohiko Sasase1), Hironobu Tadaki1), Yasuko Mera1), Yu Motohashi1), Yusuke Kemmochi2), Kaoru Toyoda2), Kochi Kakimoto2), Shinichi Kume3), and Takeshi Ohta1)

Contribution of hyperglycemia on diabetic complications in obese type 2 diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin

Yoshiaki Katsuda1), Tomohiko Sasase1), Hironobu Tadaki1), Yasuko Mera1), Yu Motohashi1), Yusuke Kemmochi2), Kaoru Toyoda2), Kochi Kakimoto2), Shinichi Kume3), and Takeshi Ohta1)
1)Biological/Pharmacological Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 1-1 Murasaki-cho, Takatsuki, Osaka 569-1125, Japan 2)Toxicology Research Laboratories, Central Pharmaceutical Research Institute, Japan Tobacco Inc., 23 Naganuki, Hadano, Kanagawa 257-0024, Japan 3)Graduate School of Agriculture, Kyoto University, Kitashirakawa Oiwake-cho, Sakyo-ku, Kyoto 606-8502, Japan
Abstract :

 The spontaneously diabetic torii (SDT) fatty rat is a new model of type 2 diabetes showing overt obesity, hyperglycemia and hyperlipidemia. With early onset of diabetes mellitus, diabetic microvascular complications, including nephropathy, peripheral neuropathy and retinopathy, are observed at young ages. In the present study, blood glucose levels of female SDT fatty rats were controlled with phlorizin, a non-selective SGLT inhibitor, to examine whether and how these complications are caused by hyperglycemia. Phlorizin treatment adequately controlled plasma glucose levels during the experiment. At 29 weeks of age, urinary albumin excretion considerably increased in SDT fatty rats. Glomerulosclerosis and tubular pathological findings also indicate diabetic nephropathy. These renal parameters tended to decrease with phlorizin; however, effects were partial. Sciatic nerve conduction velocities were significantly delayed in SDT fatty rats compared with SpragueDawley (SD) rats. Intraepidermal nerve fiber density, an indicator of subclinical small nerve fiber neuropathy, significantly decreased in SDT fatty rats. Retinal dysfunction (prolongation of peak latency for oscillatory potential in electroretinograms) and histopathological eye abnormalities, including retinal folding and mature cataracts were also observed. Both nerve and eye disorders were prevented with phlorizin. These findings indicate that severe hyperglycemia mainly causes diabetic complications in SDT fatty rats. However, other factors, such as hyperlipidemia and hypertension, may affect diabetic nephropathy. These characteristics of diabetic complications will become helpful in evaluating new drugs for diabetic complications using SDT fatty rats.

Keywords :
diabetic complications, nephropathy, peripheral neuropathy, retinopathy, SDT fatty rat

Date Deposited : 06 Jan 2016 11:34

Last Modified : 06 Jan 2016 11:34

Official URL: http://https://www.jstage.jst.go.jp/browse/expanim/64/2/_contents

Volume 64, Number 2, - 2015 , ISSN 161–169

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