| Autor: |
Patrick E MacDonald, Jean Buteau, Matthew J Merrins, Jocelyn E. Manning Fox, Ying Wayne Wang, Austin Bautista, Yaxing Jin, Sophie L Lewandowski, Tamadher A. Alghamdi, Mourad Ferdaoussi, Kunimasa Suzuki, Aliya F Spigelman, Nancy Smith, Haopeng Lin |
| Rok vydání: |
2021 |
| Předmět: |
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| DOI: |
10.2337/figshare.16435176 |
| Popis: |
SUMOylation reduces oxidative stress and preserves islet mass at the expense of robust insulin secretion. To investigate a role for the deSUMOylating enzyme sentrin-specific protease 1 (SENP1) following metabolic stress, we put pancreas/gut-specific SENP1 knockout mice (pSENP1-KO) on a high fat diet (HFD). Male pSENP1-KO mice were more glucose intolerant following HFD than littermate controls, but only in response to oral glucose. A similar phenotype was observed in females. Plasma glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like-peptide 1 (GLP-1) responses were identical in pSENP1-KO and -WT littermates, including the HFD-induced upregulation of GIP responses. Islet mass was not different, but insulin secretion and β-cell exocytotic responses to the GLP-1 receptor agonist Exendin-4 (Ex4) and GIP were impaired in islets lacking SENP1. Glucagon secretion from pSENP1-KO islets was also reduced, so we generated β-cell-specific SENP1 knockout mice (βSENP1-KO). These phenocopied the pSENP1-KO mice with selective impairment in oral glucose tolerance following HFD, preserved islet mass expansion, and impaired β-cell exocytosis and insulin secretion to Ex4 and GIP without changes in cAMP or Ca2+ levels. Thus, β-cell SENP1 limits oral glucose intolerance following HFD by ensuring robust insulin secretion at a point downstream of incretin signaling. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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