Michelle Kimple

Credentials: PhD

Position title: Associate Director, Islet Core; Associate Professor of Endocrinology

Email: mkimple@medicine.wisc.edu

Islet Biology Core Kimple Lab

My expertise is in GPCR pharmacology and mechanisms of G protein signaling in the beta-cell. My research has focused on the role of the alpha-subunit of the unique inhibitory Gz protein, Gαz, in the beta-cell. I discovered the inhibitory effects of Prostaglandin EP3 Receptor (EP3) signaling on cAMP production and downstream insulin secretion are mediated exclusively by Gαz and also discovered islet expression of EP3 and its endogenous ligand, prostaglandin E2 (PGE2), are upregulated in diabetes. These findings implicate EP3/Gαz signaling as a therapeutic target for islet dysfunction in diabetes. Together with Dawn Davis and Elizabeth Cox, I initiated a biobank for human clinical samples to be used in diabetes and obesity research as part of the “Diabetes Research Accelerator for Wisconsin” (DRAW) team. Through this initiative, we validated PGE2 as a circulating metabolite that correlates with beta-cell function and therapeutic response in mouse and human biosamples. Our team also showed human islet expression of PGE2 synthetic enzymes correlated with markers of beta-cell compensation in non-diabetic obesity. Additionally, we have recently used whole islet, real-time cAMP/Ca2+imaging assay (also to be used in the Islet Core) to discover differential effects of EP3 signaling on beta-cell second messengers and downstream insulin secretion in the healthy, non-diabetic obese, and T2D states.