Crosstalk between insulin receptor and G protein-coupled receptor signaling systems leads to Ca²+ oscillations in pancreatic cancer PANC-1 cells.
We examined crosstalk between the insulin receptor and G protein-coupled receptor (GPCR) signaling pathways in individual human pancreatic cancer PANC-1 cells. Treatment of cells with insulin (10 ng/ml) for 5 min markedly enhanced the proportion of cells that display an increase in intracellular [Ca²+] induced by picomolar concentrations of the GPCR agonist neurotensin. Interestingly, insulin increased the proportion of a subpopulation of cells that exhibit intracellular [Ca²+] oscillations in response to neurotensin at concentrations as low as 50-200 pM. Insulin enhanced GPCR-induced Ca²+ signaling in a time- and dose-dependent manner; a marked potentiation was obtained after an exposure to a concentration of 10 ng/ml for 5 min. Treatment with the mTORC1 inhibitor rapamycin abrogated the increase in GPCR-induced [Ca²+](i) oscillations produced by insulin. Our results identify a novel aspect in the crosstalk between insulin receptor and GPCR signaling systems in pancreatic cancer cells, namely that insulin increases the number of [Ca²+](i) oscillating cells induced by physiological concentrations of GPCR agonists through an mTORC1-dependent pathway.
Young
Steven H
SH
Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine and Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095-1786, USA.
Rozengurt
Enrique
E
D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism*; D045744:Cell Line, Tumor; D006801:Humans; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D046912:Multiprotein Complexes; D009496:Neurotensin / Q000378:metabolism / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D011506:Proteins; D011972:Receptor, Insulin / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors / Q000378:metabolism
D007328:Insulin; D046912:Multiprotein Complexes; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D014157:Transcription Factors; D009496:Neurotensin; D011972:Receptor, Insulin; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D002118:Calcium