Altered Expression of Insulin Signaling Proteins in Islets from T2DM Female Mice
| Autor: | Korie L. Sondgeroth, Kathy J. Lepard |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
medicine.medical_specialty
geography geography.geographical_feature_category biology Insulin receptor signaling pathway Endocrinology Diabetes and Metabolism Pancreatic islets Insulin medicine.medical_treatment AKT1 Islet Ubiquitin ligase Insulin receptor Endocrinology medicine.anatomical_structure Internal medicine Internal Medicine biology.protein medicine GLUT2 |
| Zdroj: | Diabetes. 67 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db18-314-lb |
| Popis: | With development and progression of T2DM in KKAy mice, pancreatic islets alter their expression of GLUT2, insulin and insulin receptor. The study’s goal was to identify glucoregulatory proteins in the insulin receptor signaling pathway that were early markers of islet dysfunction after 4 weeks of uncontrolled hyperglycemia. Isolated islets were pooled from 2 groups of 12 week old mice: insulin-resistant, euglycemic KK mice and insulin-resistant, hyperglycemic KKAy T2DM mice. Samples were analyzed for 40 proteins using 221 antibodies in an insulin phospho antibody array. After 4 weeks of hyperglycemia in KKAy mice, many proteins were not altered as compared to KK mice (ratio: 0.94-1.02) including insulin receptor (Phospho-Tyr1355), FOXO1A (Phospho-Ser329), PI3-kinase p85-alpha (Phospho-Tyr607), ERK1/2, PP1-alpha, and AMPK1. The phosphorylation states of some proteins were altered including AKT1 (Phosphor-Ser124) (0.77) and IRS-1 (Phosphor-Ser636) (1.25). Three proteins were then selected for ELISA analysis in islets isolated from 4, 8 (onset of T2DM), and 12 week old mice: GLUT2, iNOS (1.41) and CBL (Phospho-Tyr700) (0.78), an E3 ubiquitin ligase. GLUT2 was lower in KKAy mice at 4 weeks (KK, 4.0±0.5; KKAy, 2.3±0.3, p Disclosure K.L. Sondgeroth: None. K. LePard: None. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|