Contribution of hyperglycemia on diabetic complications in obese type 2
diabetic SDT fatty rats: effects of SGLT inhibitor phlorizin |
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Authors: | Yoshiaki KATSUDA Tomohiko SASASE Hironobu TADAKI Yasuko MERA Yu MOTOHASHI Yusuke KEMMOCHI Kaoru TOYODA Kochi KAKIMOTO Shinichi KUME Takeshi OHTA |
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Institution: | 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 |
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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 Sprague-Dawley (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. |
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Keywords: | diabetic complications nephropathy peripheral neuropathy retinopathy SDT fatty rat |
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