Islet O-GlcNAcylation Is Required for Lipid Potentiation of Insulin Secretion through SERCA2
| Autor: | Niklas E. Damberg, Eric C. Gustafson, Juan E. Abrahante, Miranda Olson, Ramkumar Mohan, Seokwon Jo, Emilyn U. Alejandro, Amber D Lockridge |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Blood Glucose medicine.medical_specialty ATPase medicine.medical_treatment Cell Type 2 diabetes Endoplasmic Reticulum General Biochemistry Genetics and Molecular Biology Article Sarcoplasmic Reticulum Calcium-Transporting ATPases 03 medical and health sciences Mice 0302 clinical medicine Internal medicine Insulin-Secreting Cells Genetic model Insulin Secretion medicine Animals Insulin Obesity lcsh:QH301-705.5 geography geography.geographical_feature_category biology Chemistry Endoplasmic reticulum Long-term potentiation medicine.disease Islet Lipids 030104 developmental biology medicine.anatomical_structure Endocrinology Diabetes Mellitus Type 2 lcsh:Biology (General) biology.protein Protein Processing Post-Translational 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol 31, Iss 5, Pp-(2020) Cell Rep |
| ISSN: | 2211-1247 |
| Popis: | Summary During early obesity, pancreatic β cells compensate for increased metabolic demand through a transient phase of insulin hypersecretion that stabilizes blood glucose and forestalls diabetic progression. We find evidence that β cell O-GlcNAcylation, a nutrient-responsive post-translational protein modification regulated by O-GlcNAc transferase (OGT), is critical for coupling hyperlipidemia to β cell functional adaptation during this compensatory prediabetic phase. In mice, islet O-GlcNAcylation rises and falls in tandem with the timeline of secretory potentiation during high-fat feeding while genetic models of β-cell-specific OGT loss abolish hyperinsulinemic responses to lipids, in vivo and in vitro. We identify the endoplasmic reticulum (ER) Ca2+ ATPase SERCA2 as a β cell O-GlcNAcylated protein in mice and humans that is able to rescue palmitate-stimulated insulin secretion through pharmacological activation. This study reveals an important physiological role for β cell O-GlcNAcylation in sensing and responding to obesity, with therapeutic implications for managing the relationship between type 2 diabetes and its most common risk factor. |
| Databáze: | OpenAIRE |
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