Mouse Pancreatic Peptide Hormones Probed at the Sub-Single-Islet Level: The Effects of Acute Corticosterone Treatment
| العنوان: | Mouse Pancreatic Peptide Hormones Probed at the Sub-Single-Islet Level: The Effects of Acute Corticosterone Treatment |
|---|---|
| المؤلفون: | Aleksandra Antevska, Connor C. Long, Samuel D. Dupuy, J. Jason Collier, Michael D. Karlstad, Thanh D. Do |
| المصدر: | Journal of Proteome Research. 22:235-245 |
| بيانات النشر: | American Chemical Society (ACS), 2022. |
| سنة النشر: | 2022 |
| مصطلحات موضوعية: | Mice, Insulin-Secreting Cells, Animals, Insulin, General Chemistry, Insulin Resistance, Corticosterone, Biochemistry |
| الوصف: | We combine liquid chromatography coupled with ion mobility spectrometry-mass spectrometry to elucidate how short exposure to corticosterone (Cort) alters the output of mouse pancreatic islet hormones. The workflow enables the robust separation of mouse insulin 1 (Ins1) and insulin 2 (Ins2) and the detection of major islet hormones in a homogenate equivalent to 100-150 islet cells. We show that Ins2 has a unique structure and is degraded much faster than Ins1. Further investigation indicates that Ins2 may populate both T and R states, whereas Ins1 may not. The assemblies of Ins1's B-chain also introduce more structural heterogeneity than Ins2. Collectively, these features account for their unique degradation profiles, the diabetes risk associated with Ins1, and the protective effect of Ins2. In the same experiments, we observe that the ratio of amylin to Ins1 increased significantly in Cort-treated mice (15:1) compared to the control mice (42:1), correlating well with β-cell proliferation observed in immunoassays on the same animal model. We observe no increase in intact full-length insulin levels but more of the truncated forms, indicating that enzymatic activity is accelerated. Our data provide a molecular basis for reduced insulin action induced by Cort and connections between insulin turnover and insulin resistance. |
| تدمد: | 1535-3907 1535-3893 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ccc0dd61a9c7cbf842765e6b4a807944 https://doi.org/10.1021/acs.jproteome.2c00668 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....ccc0dd61a9c7cbf842765e6b4a807944 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15353907 15353893 |
|---|