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SENP2 regulates mitochondrial function and insulin secretion in pancreatic β cells
Jinyan Nan1, Ji Seon Lee1, Joon Ho Moon2
1Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
Experimental & Molecular Medicine
|January 22, 2022
Summary
Small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) is crucial for pancreatic beta cell function. SENP2 deficiency impairs glucose tolerance and insulin secretion by affecting mitochondrial dynamics via DRP1 phosphorylation.
Area of Science:
- Metabolic Regulation
- Cellular Biology
- Endocrinology
Background:
- Small ubiquitin-like modifier (SUMO) modification is increasingly recognized for its role in metabolic regulation.
- SUMO-specific protease 2 (SENP2) has been previously linked to lipid metabolism and adipogenesis.
Purpose of the Study:
- To investigate the function of SENP2 in pancreatic beta cells.
- To elucidate the mechanisms by which SENP2 influences insulin secretion and mitochondrial function.
Main Methods:
- Generation of a beta cell-specific knockout mouse model (Senp2-βKO).
- Assessment of glucose tolerance and insulin secretion.
- Analysis of islet mitochondrial morphology and function (oxygen consumption).
- Investigation of DRP1 phosphorylation and SUMOylation in beta cell lines (NIT-1).
Main Results:
- Senp2-βKO mice exhibited impaired glucose tolerance and reduced glucose-stimulated insulin secretion (GSIS).
- Islets from Senp2-βKO mice showed enlarged mitochondria, decreased oxygen consumption, and reduced DRP1 phosphorylation.
- SENP2 deficiency increased SUMO2/3 conjugation to DRP1, suppressing its phosphorylation and potentially causing mitochondrial dysfunction.
- SENP2 overexpression rescued GSIS impairment and increased DRP1 phosphorylation, even under palmitate treatment.
Conclusions:
- SENP2 plays a critical role in regulating pancreatic beta cell function and insulin secretion.
- SENP2 modulates mitochondrial dynamics and function, at least partly through regulating DRP1 phosphorylation.
- Targeting SENP2 may offer therapeutic potential for metabolic disorders characterized by beta cell dysfunction.
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