Antidiabetic Effects of SGLT2-Selective Inhibitor Ipragliflozin in Streptozotocin–Nicotinamide-Induced Mildly Diabetic Mice

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概要

• 論文の詳細を見る

• Sodium-glucose cotransporter (SGLT) 2 plays an important role in renal glucose reabsorption, and inhibition of renal SGLT2 activity represents an innovative strategy for the treatment of hyperglycemia in diabetic patients. The present study investigated the antidiabetic effects of ipragliflozin, a SGLT2-selective inhibitor, in streptozotocin–nicotinamide-induced mildly diabetic mice, which exhibited a mild decline in glucose tolerance associated with the loss of early-phase insulin secretion. Oral administration of ipragliflozin increased urinary glucose excretion in a dose-dependent manner, an effect which was significant at doses of 0.3 mg/kg or higher and lasted over 12 h. In addition, ipragliflozin dose-dependently improved hyperglycemia and glucose intolerance with concomitant decreases in plasma insulin levels without causing hypoglycemia. Once-daily dosing of ipragliflozin (0.1 – 3 mg/kg) for 4 weeks attenuated hyperglycemia, glucose intolerance, and impaired insulin secretion. These results suggest that the SGLT2-selective inhibitor ipragliflozin increases urinary glucose excretion by inhibiting renal glucose reabsorption, improves hyperglycemia in streptozotocin–nicotinamide-induced mildly diabetic mice, and may be useful for treating type 2 diabetes.

• 公益社団法人 日本薬理学会の論文

著者

• Takasu Toshiyuki

  Drug Discovery Research, Astellas Pharma Inc.

• Shibasaki Masayuki

  Drug Discovery Research Astellas Pharma Inc.

• Tahara Atsuo

  Drug Discovery Research Astellas Pharma Inc.

• Kurosaki Eiji

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Yokono Masanori

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Yamajuku Daisuke

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Kihara Rumi

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Hayashizaki Yuka

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Imamura Masakazu

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• Qun Li

  Applied Pharmacology Research Laboratories, Astellas Pharma Europe B.V., The Netherlands

• Tomiyama Hiroshi

  Product Planning and Coordination Division, Research and Development Department, Kotobuki Pharmaceutical Co., Ltd., Japan

• Kobayashi Yoshinori

  Synthetic Division, Research Laboratories, Kotobuki Pharmaceutical Co., Ltd., Japan

• Noda Atsushi

  Synthetic Division, Research Laboratories, Kotobuki Pharmaceutical Co., Ltd., Japan

• Sasamata Masao

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• KIHARA Rumi

  Drug Discovery Research, Astellas Pharma, Inc.

• IMAMURA Masakazu

  Drug Discovery Research, Astellas Pharma, Inc.

• TOMIYAMA Hiroshi

  Product Planning and Coordination Division, Research and Development Department, Kotobuki Pharmaceutical Co., Ltd.

• KUROSAKI Eiji

  Drug Discovery Research, Astellas Pharma, Inc.

• SASAMATA Masao

  Drug Discovery Research, Astellas Pharma, Inc.

• Takasu Toshiyuki

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• KOBAYASHI Yoshinori

  Synthetic Division, Research Laboratories, Kotobuki Pharmaceutical Co., Ltd.

• YAMAJUKU Daisuke

  Drug Discovery Research, Astellas Pharma, Inc.

• YOKONO Masanori

  Drug Discovery Research, Astellas Pharma, Inc.

• Tahara Atsuo

  Drug Discovery Research, Astellas Pharma, Inc., Japan

• HAYASHIZAKI Yuka

  Drug Discovery Research, Astellas Pharma, Inc.

• NODA Atsushi

  Synthetic Division, Research Laboratories, Kotobuki Pharmaceutical Co., Ltd.

• QUN Li

  Applied Pharmacology Research Laboratories, Astellas Pharma Europe B. V.

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• Antidiabetic Effects of SGLT2-Selective Inhibitor Ipragliflozin in Streptozotocin–Nicotinamide-Induced Mildly Diabetic Mice
• Antidiabetic Effects of SGLT2-Selective Inhibitor Ipragliflozin in Streptozotocin-Nicotinamide-Induced Mildly Diabetic Mice

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