Oral administration of NPC43 counters hyperglycemia and activates insulin receptor in streptozotocin-induced type 1 diabetic mice
| Autor: | Alexandros Yiannikouris, Thirupathi Reddy Yerramreddy, Zi-Jian Lan, Katie Eastridge, Lucinda Nation, Zhenmin Lei, Hayley Kincaid, Ryan Goettl, Ronan Power, Xian Li, Rijin Xiao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
endocrine system mice endocrine system diseases experimental Endocrinology Diabetes and Metabolism Glucose uptake Administration Oral 030209 endocrinology & metabolism Type 2 diabetes Streptozocin Diabetes Mellitus Experimental 03 medical and health sciences 0302 clinical medicine Oral administration Internal medicine Diabetes mellitus medicine Animals Protein kinase B 030304 developmental biology 0303 health sciences biology business.industry Skeletal muscle nutritional and metabolic diseases Emerging Technologies Pharmacology and Therapeutics medicine.disease Streptozotocin Receptor Insulin Insulin receptor Endocrinology medicine.anatomical_structure Diabetes Mellitus Type 1 Diabetes Mellitus Type 2 Hyperglycemia diabetes mellitus biology.protein pharmacology business medicine.drug |
| Zdroj: | BMJ Open Diabetes Research & Care |
| ISSN: | 2052-4897 |
| Popis: | IntroductionAdenosine, 5’-Se-methyl-5’-seleno-,2’,3’-diacetate (NPC43) is a recently identified small, non-peptidyl molecule which restores normal insulin signaling in a mouse model of type 2 diabetes (Lanet al). The present study investigated the ability of NPC43 as an oral and injectable insulin-replacing agent to activate insulin receptor (INSR) and counter hyperglycemia in streptozotocin (STZ)-induced type 1 diabetic (T1D) mice.Research design and methodsIn this study, STZ was intraperitoneally injected into wild-type mice to induce hyperglycemia and hypoinsulinemia, the main features of T1D. These STZ-induced T1D mice were given NPC43 orally or intraperitoneally and blood glucose levels were measured using a glucometer. Protein levels of phosphorylated and total Insrβ, protein kinase B (Akt) and AS160 (critical for glucose uptake) in the skeletal muscle and liver of STZ-induced T1D mice following oral NPC43 treatment were determined by western blot analysis. In addition, hepatic expression of activated Insr in STZ-induced T1D mice after intraperitoneal NPC43 treatment was measured by ELISA. Student’s t-test was used for statistical analysis.ResultsOral administration of NPC43 at a dose of 5.4 or 10.8 mg/kg body weight (mpk) effectively lowered blood glucose levels in STZ-induced T1D mice at ≥1 hour post-treatment and the glucose-lowering activity of oral NPC43 persisted for 5 hours. Blood glucose levels were also reduced in STZ-induced T1D mice following intraperitoneal NPC43 (5.4 mpk) treatment. Protein levels of phosphorylated Insrβ, Akt and AS160 were significantly increased in the skeletal muscle and liver of STZ-induced T1D mice after oral NPC43 (5.4 mpk) treatment. In addition, activation of hepatic Insr was observed in STZ-induced T1D mice following intraperitoneal NPC43 (5.4 mpk) treatment.ConclusionsWe conclude that NPC43 is a de facto fast-acting oral and injectable insulin mimetic which activates Insr and mitigates hyperglycemia in a mouse model of T1D. |
| Databáze: | OpenAIRE |
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