An INS-1 ?-cell proteome highlights the role of fatty acid biosynthesis in glucose-stimulated insulin secretion

ABSTRACT: Pancreatic beta cells secrete insulin as a response to rising glucose levels in the blood, a process that is known as glucose-stimulated insulin secretion (GSIS). Although GSIS has been extensively studied, not all associated mechanisms are fully understood at the molecular level. In this study, we used liquid chromatography tandem mass spectrometry and data-independent acquisition to acquire proteomes of rat pancreatic INS-1 832/13 beta cells that were short-term stimulated with glucose concentrations ranging from 0 to 20 mM, quantifying the behavior of 3703 proteins across 11 conditions. Insulin secretion and ensemble clustering of proteome profiles revealed unique response patterns of proteins expressed by INS-1 cells. 237 proteins, amongst them proteins associated with SNARE interaction in vesicular transport, protein export, and pancreatic secretion showed an increase in abundance upon glucose stimulation, whilst the majority of proteins, including those associated with common metabolic pathways such as glycolysis, the TCA cycle and the respiratory chain, did not respond to rising glucose concentrations. Interestingly, we observe that certain proteins, for example enzymes participating in fatty acid metabolism, respond distinctly, showing a “switch-on” response upon release of glucose starvation with no further changes in abundance upon increasing glucose levels. We speculate that increased activity of fatty acid metabolic activity might either be part of GSIS by replenishing membrane lipids required for vesicle mediated exocytosis, and/or by providing an electron sink to compensate for the increase in glucose catabolism. This submission contains the raw files, the library used for the analysis, and the corresponding DIA-NN report and associated files.

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Type B Pancreatic Cell, Cell Culture

SUBMITTER: Julia Muenzner  

LAB HEAD: Markus Ralser

PROVIDER: PXD053750 | Pride | 2025-07-07

REPOSITORIES: Pride