Peripheral combination treatment of leptin and an SGLT2 inhibitor improved glucose metabolism in insulin-dependent diabetes mellitus mice
| Autor: | Daisuke Hagiwara, Runan Sun, Ryoichi Banno, Hiroshi Arima, Akira Mizoguchi, Takeshi Onoue, Taku Tsunekawa, Yoshihiro Ito, Hidetaka Suga, Shintaro Iwama, Hiroshi Yaginuma, Hiroshi Takagi, Tomoko Kobayashi, Keigo Taki, Mariko Sugiyama |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Leptin medicine.medical_specialty medicine.medical_treatment Administration Oral Thiophenes RM1-950 Carbohydrate metabolism chemistry.chemical_compound β-hydroxybutyrate Glucosides Internal medicine Diabetes mellitus medicine Animals IDDM Infusions Intravenous Sodium-Glucose Transporter 2 Inhibitors Pharmacology Glucose tolerance test Glucose metabolism medicine.diagnostic_test business.industry Insulin SGLT2 inhibitor medicine.disease Streptozotocin Mice Inbred C57BL Disease Models Animal Diabetes Mellitus Type 1 Glucose Endocrinology Ipragliflozin chemistry Molecular Medicine Drug Therapy Combination Therapeutics. Pharmacology SGLT2 Inhibitor business medicine.drug |
| Zdroj: | Journal of Pharmacological Sciences, Vol 147, Iss 4, Pp 340-347 (2021) |
| ISSN: | 1347-8613 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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