Glucose-dependent phosphorylation signaling pathways and crosstalk to mitochondrial respiration in insulin secreting cells

Cell Communication and Signaling : CCS
Jaime Santo-DomingoAndreas Wiederkehr

Abstract

Glucose is the main secretagogue of pancreatic beta-cells. Uptake and metabolism of the nutrient stimulates the beta-cell to release the blood glucose lowering hormone insulin. This metabolic activation is associated with a pronounced increase in mitochondrial respiration. Glucose stimulation also initiates a number of signal transduction pathways for the coordinated regulation of multiple biological processes required for insulin secretion. Shotgun proteomics including TiO2 enrichment of phosphorylated peptides followed by liquid chromatography tandem mass spectrometry on lysates from glucose-stimulated INS-1E cells was used to identify glucose regulated phosphorylated proteins and signal transduction pathways. Kinase substrate enrichment analysis (KSEA) was applied to identify key regulated kinases and phosphatases. Glucose-induced oxygen consumption was measured using a XF96 Seahorse instrument to reveal cross talk between glucose-regulated kinases and mitochondrial activation. Our kinetic analysis of substrate phosphorylation reveal the molecular mechanism leading to rapid activation of insulin biogenesis, vesicle trafficking, insulin granule exocytosis and cytoskeleton remodeling. Kinase-substrate enrichment identified ups...Continue Reading

References

Feb 1, 1988·The Journal of Clinical Investigation·K S PolonskyE Van Cauter
Jun 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·F C SchuitD G Pipeleers
Feb 7, 2002·Biochemical and Biophysical Research Communications·Masayoshi KatoTadaomi Takenawa
Jun 12, 2002·Molecular Biology of the Cell·Thierry CoppolaRomano Regazzi
Jul 25, 2003·Diabetologia·P Rorsman, E Renström
Feb 4, 2006·The Journal of Physiology·Dan S LucianiKenneth S Polonsky
Apr 28, 2006·International Psychogeriatrics·Marie-Pierre SylvestreMichal Abrahamowicz
Oct 3, 2007·Cell Metabolism·Carsten Schmitz-PeifferTrevor J Biden
Jul 2, 2008·Cell Metabolism·Oleg DyachokAnders Tengholm
Aug 30, 2008·Regulatory Peptides·G M Portela-GomesS K Mahata
Feb 4, 2010·PloS One·Stefanie ObermüllerSebastian Barg
Jul 9, 2010·Trends in Endocrinology and Metabolism : TEM·Jakob Suckale, Michele Solimena
Aug 26, 2010·Journal of Cell Science·Eulalia Pozo-GuisadoFrancisco Javier Martín-Romero
Dec 25, 2010·Cell·Edward L HuttlinSteven P Gygi
Dec 29, 2010·Journal of Cell Science·Hesso Farhan, Catherine Rabouille
May 3, 2011·Cell Metabolism·Andreas WiederkehrClaes B Wollheim
Jul 9, 2011·Biology of the Cell·Wei-Wei ShenNicolas Demaurex
Jul 26, 2011·Molecular and Cellular Endocrinology·Andreas Wiederkehr, Claes B Wollheim
Mar 15, 2012·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Felicia A HanzuAbdullah Sener
Jun 8, 2012·Nature Communications·Alicia LundbyJesper V Olsen
Jun 27, 2013·Diabetes·Christopher J RhodesSteven E Kahn
Jul 23, 2013·Journal of Molecular Endocrinology·Xianglan SunJiajun Zhao
Dec 12, 2013·Molecular Metabolism·Maria Grazia Magro, Michele Solimena
Feb 21, 2014·The Journal of Biological Chemistry·Umberto De MarchiAndreas Wiederkehr
Apr 1, 2014·The Journal of Endocrinology·Henrik OrtsäterÅke Sjöholm
Jul 30, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Marina KoneGuy A Rutter
Aug 20, 2015·American Journal of Physiology. Endocrinology and Metabolism·Caroline Arous, Philippe A Halban

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Citations

Feb 19, 2020·Expert Review of Proteomics·Loïc Dayon, Michael Affolter
Oct 20, 2019·Journal of Molecular Biology·Jaime Santo-DomingoAndreas Wiederkehr
Oct 2, 2021·Diabetes·Barbara E CorkeyMatthew J Merrins

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Methods Mentioned

BETA
Protein Assay
acetylation
GTPase

Software Mentioned

Scaffold
Mascot
Scaffold Q + S
ggplot
RColorBrewer
R cluster
Metacore
Proteome
KSEA
traj R

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