Matthew J. Merrins
Credentials: Metabolic regulation of insulin secretion in aging, obesity, and diabetes
Position title: Associate Professor - Department of Medicine
Email: merrins@wisc.edu
Phone: (608) 256-1901 x12848
Address:
C4134A VA Hospital (4th floor - C wing)
The Merrins Lab Website
Education
• B.A., Oberlin College
• Ph.D, University of Michigan
• Postdoctoral Fellow at University of Michigan Brehm Diabetes Center
Honors & Awards
• Ruth L. Kirschstein National Research Service Award, 2010
• NIDDK Research Scientist Development Award, 2014
• American Diabetes Association Innovative Basic Sciences Award, 2016
• Wisconsin Partnership Program New Investigator Award, 2017
• Central Society for Clinical and Translational Research Early Career Development Award, 2017
Research Interests
Keywords: metabolism, mitochondrial biology, exocytosis, insulin secretion, fluorescence microscopy, electrophysiology
Research in the Merrins laboratory centers on the control of insulin release from the endocrine pancreatic islets of Langerhans, and how this is disrupted in diabetes. Our main interests lie in two features of nutrient metabolism in islet beta cells, (1) the ability to trigger pulses of insulin release, and (2) the ability to trigger cell proliferation, when the demand for insulin increases (e.g. during aging and obesity). These adaptive responses to environmental stress ultimately fail in diabetes.
To understand how this occurs, we utilize rodent models of obesity and aging in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (FRET, optogenetics, super-resolution and FLIM/2-photon) to monitor biochemical reactions as they occur in living cells. Our recent work is focused on the design and utilization of biosensors useful for real-time measurements of glycolysis, as well as the development of NAD(P)H FLIM as a non-invasive optical approach to study the TCA cycle and electron transport chain. Using these tools, we have been able to monitor metabolite production and second messenger signaling in a variety of pathways.
Live-cell imaging of Pancreatic Islet Oscillations (movie):
Active Projects
• Regulation of pulsatile insulin secretion by pyruvate kinase M2 (PKM2), and its dynamic control by allosteric regulation and post-translational modifications.
• Mechanisms of communication between metabolism and the cell cycle mediated by cyclin dependent kinases (CDKs) and their regulators.
• Characterization of metabolic enzymes identified by RNA sequencing as type 2 diabetes-associated loci; we are using live-cell imaging to elucidate the mechanisms by which these proteins control mitochondrial fluxes, metabolic oscillations, and insulin secretion.
• Development of NAD(P)H FLIM to study metabolic defects in aging and diabetic islets.
Postdoctoral, PhD students, MD/PhD students, and undergraduates interested in pursuing research in the laboratory should contact Dr. Merrins directly at merrins@wisc.edu.
The Merrins lab is supported by the National Institute of Diabetes and Digestive and Kidney Disorders, the National Institute of Aging, and the American Diabetes Association.
Publications
Perform a customized PubMed literature search for Matthew J. Merrins
- Schaid, M.D., J.M. Harrington, G.M. Kelly, S.M. Sdao, M.J. Merrins, and M.E. Kimple. (2023). EP3 signaling is decoupled from the regulation of glucose-stimulated insulin secretion in β-cells compensating for obesity and insulin resistance. Islets, 15: 2223327.
- Emfinger, C.H., L.E. Clark, B. Yandell, K.L. Schueler, S.P. Simonett, D.S. Stapleton, K.A. Mitok, M.J. Merrins, M.P. Keller, and A.D. Attie. (2023). Novel regulators of islet function identified from genetic variation in mouse islet Ca oscillations. eLife, 12: .
- Knuth, E.R., H.R. Foster, E. Jin, and M.J. Merrins. (2023). Leucine suppresses glucagon secretion from pancreatic islets by directly modulating α-cell cAMP. bioRxiv : the preprint server for biology, .
- Keller, M.P., K.L. Hudkins, A. Shalev, S. Bhatnagar, M.A. Kebede, M.J. Merrins, D.B. Davis, C.E. Alpers, M.E. Kimple, and A.D. Attie. (2023). What the BTBR/J mouse has taught us about diabetes and diabetic complications. iScience, 26: 107036.
- Xu, W., M.M.F. Qadir, D. Nasteska, P. Mota de Sa, C.M. Gorvin, M. Blandino-Rosano, C.R. Evans, T. Ho, E. Potapenko, R. Veluthakal, F.B. Ashford, S. Bitsi, J. Fan, M. Bhondeley, K. Song, V.N. Sure, S.S.V.P. Sakamuri, L. Schiffer, W. Beatty, R. Wyatt, D.E. Frigo, X. Liu, P.V. Katakam, W. Arlt, J. Buck, L.R. Levin, T. Hu, J. Kolls, C.F. Burant, A. Tomas, M.J. Merrins, D.C. Thurmond, E. Bernal-Mizrachi, D.J. Hodson, and F. Mauvais-Jarvis. (2023). Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells. Cell reports, 42: 112529.
- Ho, T., E. Potapenko, D.B. Davis, and M.J. Merrins. (2023). A plasma membrane-associated glycolytic metabolon is functionally coupled to K channels in pancreatic α and β cells from humans and mice. Cell reports, 42: 112394.
- Foster, H.R., T. Ho, E. Potapenko, S.M. Sdao, S.M. Huang, S.L. Lewandowski, H.R. VanDeusen, S.M. Davidson, R.L. Cardone, M. Prentki, R.G. Kibbey, and M.J. Merrins. (2022). β-cell deletion of the PKm1 and PKm2 isoforms of pyruvate kinase in mice reveals their essential role as nutrient sensors for the K channel. eLife, 11: .
- Merrins, M.J., B.E. Corkey, R.G. Kibbey, and M. Prentki. (2022). Metabolic cycles and signals for insulin secretion. Cell metabolism, 34: 947-968.
- Emfinger, C.H., E. de Klerk, K.L. Schueler, M.E. Rabaglia, D.S. Stapleton, S.P. Simonett, K.A. Mitok, Z. Wang, X. Liu, J.A. Paulo, Q. Yu, R.L. Cardone, H.R. Foster, S.L. Lewandowski, J.C. Perales, C.M. Kendziorski, S.P. Gygi, R.G. Kibbey, M.P. Keller, M. Hebrok, M.J. Merrins, and A.D. Attie. (2022). β Cell-specific deletion of Zfp148 improves nutrient-stimulated β cell Ca2+ responses. JCI insight, 7: .
- Lin, H., N. Smith, A.F. Spigelman, K. Suzuki, M. Ferdaoussi, T.A. Alghamdi, S.L. Lewandowski, Y. Jin, A. Bautista, Y.W. Wang, J.E. Manning Fox, M.J. Merrins, J. Buteau, and P.E. MacDonald. (2021). β-Cell Knockout of SENP1 Reduces Responses to Incretins and Worsens Oral Glucose Tolerance in High-Fat Diet-Fed Mice. Diabetes, 70: 2626-2638.