Biological and Pharmaceutical Bulletin

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Volume 41 (2018) Issue 5 Pages 761-769

Protective Effect of Ipragliflozin on Pancreatic Islet Cells in Obese Type 2 Diabetic db/db Mice

Toshiyuki Takasu, Shoji Takakura

Ipragliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that increases urinary glucose excretion and subsequently improves hyperglycemia in patients with type 2 diabetes mellitus (T2DM). To assess the beneficial effect of ipragliflozin on the mass and function of pancreatic β-cells under diabetic conditions, obese T2DM db/db mice were treated with ipragliflozin for 5 weeks. Glucose and lipid metabolism parameters, pathological changes in pancreatic islet cells and insulin content were evaluated. Pathological examination of pancreatic islet cells comprised measuring the ratios of insulin- and glucagon-positive cells and levels of oxidative stress markers. Hemoglobin A1c, plasma glucose, non-esterified fatty acid and triglyceride levels in ipragliflozin-treated groups were reduced compared to the diabetic control (DM-control) group. Histopathological examination of pancreatic islet cells revealed strong insulin staining and reduced glucagon staining in the ipragliflozin 10 mg/kg-treated group compared with the DM-control group. The ratio of α- to β-cell mass was lower in the ipragliflozin 10 mg/kg-treated group than the DM-control group and was similar to that of the non-diabetic control group. The density of immunostaining for 4-hydroxy-2-nonenal, an oxidative stress marker, in pancreatic islets was significantly lower in the ipragliflozin 10 mg/kg-treated group than the DM-control group. Pancreatic insulin content tended to be higher in the ipragliflozin-treated groups than the DM-control group. Our findings demonstrate the benefit of ipragliflozin treatment in improving glucolipotoxicity and reducing oxidative stress in pancreatic islet cells. Treatment with ipragliflozin may protect against the progressive loss of islet β-cells in patients with T2DM.

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Ipragliflozin is a selective sodium glucose cotransporter 2 inhibitor that increases urinary glucose excretion, and subsequently improves glucolipotoxicity. The article by Takasu et al. demonstrated that the treatment with ipragliflozin decreased pancreatic cells positive for 4-hydroxy-2-nonenal (4HNE), an oxidative stress marker, in obese type 2 diabetes mellitus (DM) db/db mice. Histopathological examination of pancreatic islet cells revealed strong insulin staining, whereas reduced glucagon staining, accordingly pancreatic insulin content tended to be higher in the ipragliflozin 10 mg/kg-treated group compared with the DM-control group. It was demonstrated that ipragliflozin has a protective effect on the pancreas by reducing oxidative stress.

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Volume 41 (2018) Issue 5

Protective Effect of Ipragliflozin on Pancreatic Islet Cells in Obese Type 2 Diabetic db/db Mice Toshiyuki Takasu, Shoji Takakura
Induction of Apoptosis by Citrus unshiu Peel in Human Breast Cancer MCF-7 Cells: Involvement of ROS-Dependent Activation of AMPK Min Yeong Kim, Hyun Hwang Bo, Eun Ok Choi, Da He Kwon, Hong Jae Kim, Kyu Im Ahn, Seon Yeong Ji, Jin-Woo Jeong, Shin-Hyung Park, Su-Hyun Hong, Gi-Young Kim, Cheol Park, Heui-Soo Kim, Sung-Kwon Moon, Seok-Joong Yun, Wun Jae Kim, Yung Hyun Choi
Sphingoid Base-Upregulated Caspase-14 Expression Involves MAPK Yukitoshi Nagahara, Kei Kawakami, Abudubari Sikandan, Daiki Yagi, Ryo Nishikawa, Takahisa Shinomiya
Development and Evaluation of Antibody Proteomics Technology for Rapid and Comprehensive Identification of Potential Biomarkers and Therapeutic Targets Kazuya Nagano

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