Matthew J. Merrins, PhD
Cards
Contact Info
Appointments
Merrins Lab
Contact Info
Appointments
Merrins Lab
Contact Info
Appointments
Merrins Lab
About
Copy Link
Titles
Joseph F. Hoffman Professor of Cellular and Molecular Physiology
Biography
Matthew J. Merrins, PhD is a Professor of Cellular & Molecular Physiology at the Yale School of Medicine. His research is focused on understanding how nutrient sensing is coupled to hormone secretion in pancreatic islet cells. A major focus of the lab is the use of fluorescence microscopy to study cellular metabolism in real time. The laboratory has expertise in several different imaging modalities including spinning disk confocal, TIRF, STED, multi-photon, and light-sheet microscopy. Dr. Merrins is best known for his work on β-cell glucose sensing, including the discovery that glycolytic metabolons, rather than mitochondria, locally generate the signal to initiate insulin secretion. Translational research in the laboratory is focused on targeting the glycolytic enzyme pyruvate kinase for the treatment of metabolic disorders. Dr. Merrins participates in multiple graduate programs, and his trainees have gone on to successful careers in research and STEM education. In the classroom, Dr. Merrins has taught endocrinology and metabolism to undergraduate, graduate, and medical students. Dr. Merrins is an academic co-founder of State 4 Therapeutics, an emerging Yale-based obesity pharmacotherapeutics company.
Appointments
Cellular & Molecular Physiology
ProfessorPrimary
Other Departments & Organizations
Education & Training
- Postdoctoral Fellow
- University of Michigan (2014)
- PhD
- University of Michigan, Physiology (2008)
- BA
- Oberlin College, Biochemistry & Biology (Honors) (2001)
Research
Copy Link
Overview
Islet biology, metabolism, mitochondria, GPCRs, type 2 diabetes, obesity, electrophysiology, live-cell imaging among research interests.
Medical Research Interests
ORCID
0000-0003-1599-9227- View Lab Website
Merrins Lab
Research at a Glance
Yale Co-Authors
Publications Timeline
Research Interests
Richard Kibbey, MD, PhD
Jing Hughes, MD, PhD
Raghav Sehgal, PhD
Obesity
Diabetes Mellitus, Type 2
Electrophysiology
Receptors, G-Protein-Coupled
Publications
2026
Amino Acid Sensing by the α-Cell Mitochondrial Phosphoenolpyruvate Cycle Regulates Intracellular Ca2+ Levels Without Affecting Glucagon Secretion.
Jin E, Foster H, Potapenko E, Huang S, Dong X, Hughes J, Merrins M. Amino Acid Sensing by the α-Cell Mitochondrial Phosphoenolpyruvate Cycle Regulates Intracellular Ca2+ Levels Without Affecting Glucagon Secretion. Diabetes 2026, 75: 483-493. PMID: 41525135, PMCID: PMC12928745, DOI: 10.2337/db25-0510.Peer-Reviewed Original ResearchAltmetricMeSH Keywords and ConceptsConceptsAmino acid sensingPresence of glutaminePhosphoenolpyruvate cyclePyruvate kinase activityAmino acidsKinase activityPyruvate kinaseA cellsAcid sensingAmino acid sensorsPhosphoenolpyruvate carboxykinase 2Response to amino acidsPyruvate kinase MTEPP-46Membrane depolarizationGlucagon secretionPEP carboxykinasePhosphoenolpyruvateKATP channelsIntracellular Ca2AminoB cellsPyruvateLeucinePancreatic islets
2025
Compartmentalized nutrient and hormone sensing in β-cells: the role of cilia
Hughes J, Merrins M. Compartmentalized nutrient and hormone sensing in β-cells: the role of cilia. Physiology 2025 PMID: 41432705, PMCID: PMC12875570, DOI: 10.1152/physiol.00042.2025.Peer-Reviewed Original ResearchConceptsPrimary ciliaSpecialized subcellular compartmentsPancreatic B-cellsRelevance to physiologyB cellsCytosolic Ca<Gene perturbationsGenetic dataSubcellular compartmentsSensory organellesStimulus-secretion couplingB cell biologyHormone sensingSignaling roleMolecular studiesFunctional studiesCiliaHormonal inputsInsulin secretionHormone receptorsInsulin releaseAcute functionMetabolic unitNutrientsExocytosis1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion
RUZ-MALDONADO I, CARDONE R, MERRINS M, KIBBEY R. 1824-P: Bioenergetic Advantage of Pyruvate Kinase Overcomes Mitochondrial OXPHOS in Beta-Cells to Initiate Insulin Secretion. Diabetes 2025, 74 DOI: 10.2337/db25-1824-p.Peer-Reviewed Original ResearchConceptsPyruvate kinaseATP/ADP ratioMitochondrial OXPHOSHuman isletsBeta-cellsIntact miceOxygen consumption rateKATP channel closureInsulin secretionMitochondrial membrane potentialPlasma membrane depolarizationDose-dependent mannerIntramitochondrial ADPADP availabilityHyperpolarized mitochondriaInitial insulin secretionKATP channelsMitochondrial hyperpolarizationOXPHOS inhibitionINS-1Pyruvate metabolismETC complexesMembrane depolarizationATP synthesisOXPHOS83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment
KIBBEY R, CARDONE R, RUZ-MALDONADO I, ZHAO X, BROWN S, FOSTER H, MERRINS M. 83-OR: GLP-1RA Efficacy Doubled with Small Molecule Modulators of Pyruvate Kinase for Obesity Treatment. Diabetes 2025, 74 DOI: 10.2337/db25-83-or.Peer-Reviewed Original ResearchConceptsGLP-1 RAsLean massCombo groupInsulin secretionOptimal treatment of obesityPreservation of lean massObesity treatmentTreatment groupsIslet healthCa2+ oscillationsCa2+ imagingFasting glucose levelsC57BL/6J male miceTreatment of obesityImproved insulin sensitivityGLP-1RAAUC glucoseOptimal treatmentDIO miceMale miceStudy endPlaceboGLP-1Body compositionInsulin sensitivityβ-cell Gɑs signaling is critical for physiological and pharmacological enhancement of insulin secretion
Capozzi M, Bouslov D, Sargsyan A, Chan M, Chen A, Gray S, Viloria K, Bareja A, Douros J, Lewandowski S, Tong J, Hasib A, Cuozzo F, Ross E, Foster M, Weinstein L, Hussain M, Merrins M, Willard F, Huising M, Sloop K, Hodson D, D’Alessio D, Campbell J. β-cell Gɑs signaling is critical for physiological and pharmacological enhancement of insulin secretion. Journal Of Clinical Investigation 2025, 135: e183741. PMID: 40526441, PMCID: PMC12352888, DOI: 10.1172/jci183741.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsIncretin-stimulated insulin secretionIncretin receptorsImpaired response to glucoseInsulin secretionGeneration of intracellular cAMPGA signalingGAS proteinsIncretin signalingImpairment of insulin secretionIncretin receptor agonistsSignaling nodePharmacological enhancementResponse to glucoseGlucagon-like peptide-1 receptorG-proteinGlucose-dependent insulinotropic polypeptideB cell deletionCell secretionEnhancement of insulin secretionDeletionPeptide-1 receptorIntracellular cAMPInsulin contentProteinReceptor agonistsCRISP: correlation-refined image segmentation process
Briggs J, Jin E, Merrins M, Benninger R. CRISP: correlation-refined image segmentation process. BMC Bioinformatics 2025, 26: 135. PMID: 40419943, PMCID: PMC12105354, DOI: 10.1186/s12859-025-06150-z.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsImage segmentation processCell masksMask refinementInterpixel correlationArea under the receiver operating curveTraining dataImage segmentationReceiver operating curveSegmentation processRecording of cellular activityAutomatic image segmentationOperating curveThresholding algorithmModel performanceUser errorsTransparent algorithmsReal-time recordingCalcium imagingMouse modelIndividual cellsAxis identificationAlgorithmPacked tissuesData setsInterpixelGlucokinase activity controls peripherally located subpopulations of β-cells that lead islet Ca2+ oscillations
Jin E, Briggs J, Benninger R, Merrins M. Glucokinase activity controls peripherally located subpopulations of β-cells that lead islet Ca2+ oscillations. ELife 2025, 13: rp103068. PMID: 39936635, PMCID: PMC11820133, DOI: 10.7554/elife.103068.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsGlucokinase activity controls peripherally located subpopulations of β-cells that lead islet Ca2+ oscillations
Jin E, Briggs J, Benninger R, Merrins M. Glucokinase activity controls peripherally located subpopulations of β-cells that lead islet Ca2+ oscillations. ELife 2025, 13 DOI: 10.7554/elife.103068.3.Peer-Reviewed Original ResearchCitations
2024
Author Correction: Intra-islet α-cell Gs signaling promotes glucagon release
Liu L, EI K, Dattaroy D, Barella L, Cui Y, Gray S, Guedikian C, Chen M, Weinstein L, Knuth E, Jin E, Merrins M, Roman J, Kaestner K, Doliba N, Campbell J, Wess J. Author Correction: Intra-islet α-cell Gs signaling promotes glucagon release. Nature Communications 2024, 15: 6383. PMID: 39075062, PMCID: PMC11286759, DOI: 10.1038/s41467-024-50810-2.Peer-Reviewed Original ResearchIntra-islet α-cell Gs signaling promotes glucagon release
Liu L, El K, Dattaroy D, Barella L, Cui Y, Gray S, Guedikian C, Chen M, Weinstein L, Knuth E, Jin E, Merrins M, Roman J, Kaestner K, Doliba N, Campbell J, Wess J. Intra-islet α-cell Gs signaling promotes glucagon release. Nature Communications 2024, 15: 5129. PMID: 38879678, PMCID: PMC11180188, DOI: 10.1038/s41467-024-49537-x.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsGlucagon releaseGs signalingA cellsGlucagon secretionGs-coupled receptorsClasses of therapeutic agentsA2A adenosine receptorsPathophysiology of diabetesIslet glucagon contentAutocrine/paracrine roleKnockout miceAdenosine receptorsMouse modelPancreatic A cellsSignaling pathwayTherapeutic agentsGlucagon contentTherapeutic purposesGlucagonPotential targetReceptorsSecretionPotential importanceReleasePathophysiology
Academic Achievements & Community Involvement
Copy Link
Get In Touch
Copy Link
Contacts
Locations
300 George Street
Academic Office
Rm 2304
New Haven, CT 06511
300 George Street
Lab
Rm 2320
New Haven, CT 06511