Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice
We investigated whether peripheral combination treatment of a sodium–glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptoz...
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Elsevier
2021-12-01
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Series: | Journal of Pharmacological Sciences |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861321000852 |
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doaj-dd7741f0549c4765a056b105a4c5db1b |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hiroshi Yaginuma Ryoichi Banno Runan Sun Keigo Taki Akira Mizoguchi Tomoko Kobayashi Mariko Sugiyama Taku Tsunekawa Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Yoshihiro Ito Shintaro Iwama Hidetaka Suga Hiroshi Arima |
spellingShingle |
Hiroshi Yaginuma Ryoichi Banno Runan Sun Keigo Taki Akira Mizoguchi Tomoko Kobayashi Mariko Sugiyama Taku Tsunekawa Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Yoshihiro Ito Shintaro Iwama Hidetaka Suga Hiroshi Arima Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice Journal of Pharmacological Sciences SGLT2 inhibitor Leptin IDDM Glucose metabolism β-hydroxybutyrate |
author_facet |
Hiroshi Yaginuma Ryoichi Banno Runan Sun Keigo Taki Akira Mizoguchi Tomoko Kobayashi Mariko Sugiyama Taku Tsunekawa Takeshi Onoue Hiroshi Takagi Daisuke Hagiwara Yoshihiro Ito Shintaro Iwama Hidetaka Suga Hiroshi Arima |
author_sort |
Hiroshi Yaginuma |
title |
Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
title_short |
Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
title_full |
Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
title_fullStr |
Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
title_full_unstemmed |
Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
title_sort |
peripheral combination treatment of leptin and an sglt2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2021-12-01 |
description |
We investigated whether peripheral combination treatment of a sodium–glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 μg/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin. |
topic |
SGLT2 inhibitor Leptin IDDM Glucose metabolism β-hydroxybutyrate |
url |
http://www.sciencedirect.com/science/article/pii/S1347861321000852 |
work_keys_str_mv |
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doaj-dd7741f0549c4765a056b105a4c5db1b2021-09-13T04:13:13ZengElsevierJournal of Pharmacological Sciences1347-86132021-12-011474340347Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus miceHiroshi Yaginuma0Ryoichi Banno1Runan Sun2Keigo Taki3Akira Mizoguchi4Tomoko Kobayashi5Mariko Sugiyama6Taku Tsunekawa7Takeshi Onoue8Hiroshi Takagi9Daisuke Hagiwara10Yoshihiro Ito11Shintaro Iwama12Hidetaka Suga13Hiroshi Arima14Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464-0814, Japan; Corresponding author. Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya 464-0814, Japan. Fax: +81 52 789 3961.Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya 491-8558, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Department of Endocrinology and Diabetes, Ichinomiya Municipal Hospital, 2-2-22 Bunkyo, Ichinomiya 491-8558, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, Japan; Department of CKD Initiatives/Nephrology, Nagoya University Graduate School of Medicine, Japan Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanDepartment of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya 466-8560, JapanWe investigated whether peripheral combination treatment of a sodium–glucose cotransporter 2 (SGLT2) inhibitor and leptin improves glucose metabolism in insulin-dependent diabetes mellitus (IDDM) model mice. Twelve-week-old male C57BL6 mice were intraperitoneally administered a high dose of streptozotocin to produce IDDM. IDDM mice were then divided into five groups: SGLT2 inhibitor treatment alone, leptin treatment alone, leptin and SGLT2 inhibitor co-treatment, untreated IDDM mice, and healthy mice groups. The blood glucose (BG) level at the end of the dark cycle was measured, and a glucose tolerance test (GTT) was performed and compared between the five groups. Leptin was peripherally administered at 20 μg/day using an osmotic pump, and an SGLT2 inhibitor, ipragliflozin, was orally administered at 3 mg/kg/day. Monotherapy with SGLT2 inhibitor or leptin significantly improved glucose metabolism in mice as evaluated by BG and GTT compared with the untreated group, whereas the co-treatment group with SGLT2 inhibitor and leptin further improved glucose metabolism as compared with the monotherapy group. Notably, glucose metabolism in the co-treatment group improved to the same level as that in the healthy mice group. Thus, peripheral combination treatment with leptin and SGLT2 inhibitor improved glucose metabolism in IDDM mice without the use of insulin.http://www.sciencedirect.com/science/article/pii/S1347861321000852SGLT2 inhibitorLeptinIDDMGlucose metabolismβ-hydroxybutyrate |