Matthew J. Merrins, PhD
Department of Medicine, Division of Endocrinology, Diabetes, & Metabolism
Department of Biomolecular Chemistry (Merrins Lab Biomolecular Chemistry Webpage)
Office: C4134 VA Hospital (4th floor - C wing)
Lab: C4141 VA Hospital (4th floor - C wing)
Shipping: VA Research 151, Room C3127, Madison, WI 53705
- B.A., Oberlin College
- Ph.D., University of Michigan
- Postdoctoral Fellow, 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 Science Award, 2016
- Wisconsin Partnership Program New Investigator Award, 2017
- Central Society for Clinical and Translational Research Early Career Development Award, 2017
Research in our laboratory focuses on metabolic signaling in the pancreatic islets of Langerhans. As metabolic sensors for the organism, islets regulate blood glucose by releasing the hormones insulin and glucagon. Our main interests lie in two features of nutrient metabolism in islet cells, (1) the ability to trigger pulses of insulin release, and (2) the ability to fine-tune hormone secretion through cell-cell communication. To understand how these processes adapt to environmental stress, we utilize mouse models of obesity/diabetes in combination with biochemistry, patch clamp electrophysiology, and quantitative imaging. A central focus of the lab is the use of fluorescence microscopy (3D light-sheet imaging, optogenetics, and 2-photon microscopy) to monitor biochemical reactions as they occur in living cells.
- Regulation of pulsatile insulin secretion by pyruvate kinases
There are three isoforms of PK expressed in the pancreatic islets cells – constitutively active PKM1, and the dynamically regulated isoforms PKM2 and PKL. We are working to understand how these crucial glycolytic enzymes control metabolic and electrical activity in beta cells.
- Communication between metabolism and the cell cycle machinery
Currently we are studying the effects of two cyclin-dependent kinases, CDK1 and CDK2, on beta cell mitochondrial metabolism and electrical activity. These kinases are responsive to age and obesity, two major risk factors for diabetes.
- Nutrient regulation of islet cell-cell communication: 3D light-sheet imaging and optogenetics
To understand precisely how nutrients control hormone secretion, the goals of this project are: 1) measure the activity of every islet cell, 2) manipulate the activity of every cell, and 3) computationally analyze/model these circuits and their failure in diabetes. We've constructed a 3D light-sheet microscope capable of recording biosensors in intact islets at speeds up to 10 Hz, while stimulating or repressing islet cell activity using optogenetics.
Postdoctoral, PhD students, and undergraduates interested in pursuing research in the laboratory should contact Dr. Merrins directly at firstname.lastname@example.org.
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 of note (full publication list)
- Douros J, Niu J, Sdao SM, Gregg T, Merrins MJ, Campbell JE, Tong J, and D’Alessio DD (2019) “Temporal plasticity of insulin and incretin secretion and insulin sensitivity following sleeve gastrectomy contribute to sustained improvements in glucose control” Molecular Metabolism S2212-8778(19)30433-8. PMID: 31326351.
- Douros J, Niu J, Sdao SM, Gregg T, Fisher-Wellman K, Bharadwaj M, Molina A, Arumugam R, Martin M, Petretto E, Merrins MJ, Herman MA, Tong J, Campbell JE, and D’Alessio DD (2019) “Sleeve gastrectomy rapidly enhances islet function independent of body weight” JCI Insight 21;4(6). PMID: 30777938.
- Capozzi ME, Svendsen B, Encisco SE, Lewandowski SL, Martin MD, Lin H, Coch RW, Haldeman JM, MacDonald PE, Merrins MJ, D’Alessio DA, and Campbell JE (2019) “β-cell tone is defined by proglucagon peptides through cyclic AMP signaling” JCI Insight 7;4(5). PMID: 30720465.
- Gregg T*, Sdao SM*, Dhillon RS, Rensvold JW, Lewandowski SL, Pagliarini DJ, Denu JM, and Merrins MJ (2019) “Obesity-Dependent CDK1 Signaling Stimulates Mitochondrial Respiration at Complex I in Pancreatic β-cells” Journal of Biological Chemistry 22;294(12). PMID: 30700550. #Corresponding author
- De Leon ER, Gregg TA, Brinkman J, Fenske RJ, Schmidt BA, Kimple ME, Lamming DW#, and Merrins MJ# (2018) “Age-Dependent Protection of Insulin Secretion in Diet Induced Obese Mice” Scientific Reports 8(1), 17814. PMID: 30546031. #Corresponding author
- Hennings TG, Chopra DG, De Leon ER, VanDeusen HR, Choe JJ, Sesaki HS, Merrins MJ, and Ku G (2018) “In vivo Deletion of β-cell Drp1 Impairs Insulin Secretion without Affecting Islet Oxygen Consumption” Endocrinology. PMID: 30052866.
- Sharick JT, Favreau PF, Gilette AA, Sdao SM, Merrins MJ, and Skala MC (2018) “Protein-bound NAD(P)H Lifetime is Sensitive to Multiple Fates of Glucose Carbon” Scientific Reports 8(1), 5456. PMID: 29615678.
- Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, and Lamming DW (2017) “Restoration of Metabolic Health by Decreased Consumption of Branched-Chain Amino Acids” Journal of Physiology. Dec 19. PMID: 29266268.
- Hernandez R, Graves SA, Gregg T, VanDeusen HR, England CG, Valdovinos HF, Jeffery JJ, Barnhart TE, Severin GW, Nickles RJ, Merrins MJ#, and Cai W# (2017) “Assessing Functional β-cell Mass with Radiomanganese PET” Diabetes 66(8), 2163-2174. PMID: 28515126. #Corresponding authors.
- Neuman JC, Schaid MD, Brill AL, Fenske RJ, Kibbe CR, Fontaine DA, Sdao SM, Brar HK, Connors KM, Wienkes HN, Eliceiri KW, Merrins MJ, Davis DB, and Kimple ME (2017) “Enriching Islet Phospholipids with Eicosapentaenoic Acid Reduces Prostaglandin E2 Signaling and Enhances Diabetic β-cell Function” Diabetes 66(6), 1572-1585. PMID: 28193789.
- Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Fiigenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, and Lamming DW (2016) “Decreased Consumption of Branched Chain Amino Acids Improves Metabolic Health” Cell Reports 16(2), 520-530. PMID: 27346343.
- Gregg T, Poudel C, Schmidt BA, Dhillon RS, Sdao SM, Truchan NA, Baar EL, Fernandez LA, Denu JM, Eliceiri KW, Rogers JD, Kimple ME, Lamming DW, and Merrins MJ (2016) “Pancreatic β-cells from Mice Offset Age-Associated Mitochondrial Deficiency with Reduced KATP Channel Activity” Diabetes 65(9), 2700-2710. PMID: 27284112.
- Kim SY, Lee JH, Merrins MJ, Gavrilova O, Bisteau X, Kaldis P, Satin LS, and Rane SG (2017) “Loss of Cyclin Dependent Kinase 2 in the Pancreas Links Primary β-cell Dysfunction to Progressive Depletion of β‑cell Mass and Diabetes” Journal of Biological Chemistry 292(9), 3841-3853. PMID: 28100774.
- McKenna J, Ha J, Merrins MJ, Sherman A, Satin LS, and Bertram R (2016) “Ca2+ Effects on ATP Production and Consumption Have Key Regulatory Roles on Oscillatory Islet Activity” Biophysical Journal 110, 733-742. PMID: 26840737.
- Merrins MJ, Poudel C, McKenna JP, Ha J, Sherman A, Bertram R, and Satin LS (2016) “Phase Analysis of Metabolic Oscillations and Membrane Potential in Pancreatic β-cells” Biophysical Journal 110, 691–699. PMID: 27129239.
- Merrins MJ, Van Dyke AR, Mapp AK, Rizzo MA, Satin LS (2013) “Direct measurements of oscillatory glycolysis in pancreatic islet β-cells using novel FRET biosensors for pyruvate kinase M2 activity” Journal of Biological Chemistry 288, 33312–33322. PMID: 24100037.
- Merrins MJ, Bertram R, Sherman A, Satin LS (2012) “Phosphofructo-2-kinase/fructose-2,6-bisphosphatase modulates oscillations of pancreatic islet metabolism” PLOS one 7, e34036. PMID: 22532827.
- Merrins MJ, Fendler B, Zhang M, Sherman A, Bertram R, Satin LS (2010) “Metabolic oscillations in pancreatic islets depend on the intracellular Ca2+ level but not Ca2+ oscillations” Biophysical Journal 99, 76–84. PMID: 20655835.
- Merrins MJ and Stuenkel EL (2008) “Kinetics of Rab27a-dependent actions on vesicle docking and priming in pancreatic β-cells” Journal of Physiology 586, 5367–5381. PMID: 18801842.
- Highlighted in: Ullrich S. (2008) “Glucose-induced insulin secretion: is the small G-protein Rab27A the mediator of the KATP channel-independent effect?” Journal of Physiology 586, 5291. PMID: 19011133.