1 RIPK2 dictates insulin responses to tyrosine kinase inhibitors in obese mice Brittany M. Duggan 1 , Joseph F. Cavallari 1 , Kevin P. Foley 1 , Nicole G. Barra 1 , Jonathan D. Schertzer 1* 1 Department of Biochemistry and Biomedical Sciences and Farncombe Family Digestive Health Research Institute, Centre for Metabolism, Obesity and Diabetes Research, McMaster University, 1200 Main St. W., Hamilton, Ontario, Canada L8N 3Z5 Corresponding author*: Jonathan D. Schertzer Associate Professor McMaster University Faculty of Health Sciences Department of Biochemistry and Biomedical Sciences HSC 4H19 1200 Main St West Hamilton, ON, Canada L8N 3Z5 Tel: 905 525 9140 x. 22254 Fax: 905 525-9033 *Please address reprint requests to corresponding author Short title: TKIs alter insulin via RIPK2 Keywords: metabolic inflammation, tyrosine kinase inhibitors, insulin resistance, obesity, diabetes Figures: 10 Financial support: This work was supported by a Natural Sciences and Engineering Research Council of Canada (NSERC) discovery grant with an early career researcher supplement from NSERC. BMD was supported by Ontario Graduate Scholarships. JFC was supported by a Farncombe Family postdoctoral fellowship. JDS holds a Canada Research Chair in Metabolic Inflammation. KPF was supported by a NSERC fellowship. Disclosure: The authors have nothing to disclose. Abbreviations: TKIs, tyrosine kinase inhibitors; PRRs, pattern recognition receptors; TLRs, Toll-like receptors; NLRs, Nod-like receptors; MDP, muramyl dipeptide; PDGFRβ, platelet- derived growth factor receptor β; CD, control diet; HFD, high fat diet; GTT, glucose tolerance test; ITT, insulin tolerance test, OGSIS, oral glucose-stimulated insulin secretion