Abstract
Protein acetylation has a crucial role in energy metabolism. Here we performed the first large-scale profiling of acetylome in rat islets, showing that almost all enzymes in core metabolic pathways related to insulin secretion were acetylated. Label-free quantitative acetylome of islets in response to high glucose revealed hyperacetylation of enzymes involved in fatty acid β-oxidation (FAO), including trifunctional enzyme subunit alpha (ECHA). Acetylation decreased the protein stability of ECHA and its ability to promote FAO. The overexpression of SIRT3, a major mitochondrial deacetylase, prevented the degradation of ECHA via decreasing its acetylation level in β-cells. SIRT3 expression was upregulated in rat islets upon exposure to low glucose or fasting. SIRT3 overexpression in islets markedly decreased palmitate-potentiated insulin secretion, whereas islets from SIRT3 knockout mice secreted more insulin, with an opposite action on FAO. ECHA overexpression partially reversed SIRT3 deficiency-elicited insulin hypersecretion. Our study highlights the potential role of protein acetylation in insulin secretion.
Highlights
Pancreatic β-cells display a great degree of plasticity to secrete insulin in response to nutrient availability[1,2]
Impact of histone deacetylases (HDACs) inhibition on insulin secretion in rat islets To directly evaluate the role of protein acetylation in islet function, we investigated the combined effect of two HDAC inhibitors, trichostatin A (TSA), and NAM, on insulin secretion
Insulin secretion in the presence of 3.3 mM glucose was markedly elicited with prolonged treatment of TSA and NAM (Fig. 1b)
Summary
Pancreatic β-cells display a great degree of plasticity to secrete insulin in response to nutrient availability[1,2]. Many metabolic coupling factors have been proposed to modulate metabolic networks involved in fuel-induced insulin secretion, the enormous complexity of metabolism-triggered signaling processes is beyond our understanding[3]. The growing landscape of protein posttranslational modification (PTM) has highlighted its regulatory roles in cellular metabolism[4]. Acetylation level is tightly governed by lysine acetyltransferases (KATs) and deacetylases (KDACs)[12]. All KATs require acetyl-CoA as substrate for acetylation reactions. Another intermediary metabolite NAD+ directly alters KDAC activities to link energy status to cellular homeostasis, making acetylation especially favorable in regulating metabolic enzymes.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
