期刊
LIFE SCIENCES
卷 76, 期 23, 页码 2655-2668出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2004.09.038
关键词
T-1095; antidiabetic agent; Na+-glucose cotransporter; type 2 diabetes; GK rat; insulin resistance; neuropathy
We examined the effects of T-1095, an orally active inhibitor of Na+-glucose cotransporter (SGLT), on the development and severity of diabetes in Goto-Kakizaki (GK) rat, a spontaneous, non-obese model of type 2 diabetes. T-1095 was administered as dietary admixture (0.1% w/w) beginning at 7 weeks of age for 32 weeks. Untreated male GK rats were hyperglycemic compared with Wistar rats. Throughout the study, T-1095 treatment significantly decreased both blood glucose and hemoglobin Ate levels in the GK rats. The concomitant increase of urinary glucose excretion indicated that the hypoglycemic action of T-1095 is derived from the enhancement of urinary glucose disposal. Although food intake was not changed in the T-1095-treated rats, the body weight gain was retarded. T-1095 treatment partially ameliorated oral glucose tolerance but not the impaired glucose-induced insulin secretion. Homeostasis model assessment (HOMA) indicated the existence of insulin resistance in GK rats and a significant restoration by T-1095-treatment. There was a reduction of the thermal response in tail-flick testing following long-term hyperglycemia (diabetic neuropathy). Treatment of T-1095 significantly prevented the development of diabetic neuropathy in male GK rats. Sustained improvement of hyperglycemia and prevention of diabetic neuropathy by the T-1095-treatment provide further support the use of SGLT inhibitors for the treatment of diabetes. (c) 2005 Elsevier Inc. All rights reserved.
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