Matthew J. Merrins, PhD
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Merrins Lab
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Merrins Lab
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Merrins Lab
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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
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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 ResearchThis study investigates how amino acid sensing in pancreatic α-cells via the mitochondrial phosphoenolpyruvate cycle regulates calcium levels but does not influence glucagon secretion, which is crucial for understanding diabetes-related glucagon dysregulation.
2025
Compartmentalized Nutrient and Hormone Sensing in β-Cells: the Role of Primary Cilia
Hughes J, Merrins M. Compartmentalized Nutrient and Hormone Sensing in β-Cells: the Role of Primary Cilia. Physiology 2025, 41: 000-000. PMID: 41432705, PMCID: PMC12875570, DOI: 10.1152/physiol.00042.2025.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsThis study reviews how primary cilia in pancreatic beta cells influence insulin secretion by sensing nutrients and hormones, highlighting their potential role in diabetes.β-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.Commentaries, Editorials and LettersIntra-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 importanceReleasePathophysiologyLeucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling.
Knuth E, Foster H, Jin E, Ekstrand M, Knudsen J, Merrins M. Leucine Suppresses α-Cell cAMP and Glucagon Secretion via a Combination of Cell-Intrinsic and Islet Paracrine Signaling. Diabetes 2024, 73: 1426-1439. PMID: 38870025, PMCID: PMC11333377, DOI: 10.2337/db23-1013.Peer-Reviewed Original ResearchCitationsAltmetricMeSH Keywords and ConceptsConceptsNutrient regulationCombination of cell-intrinsicMouse isletsA cellsPresence of elevated glucoseGlucose dose-dependentlyRegulation of glucagon releaseGlucagon secretionPhysiological concentrationsParacrine signalingIncretins GIPFatty acid oxidationMitochondrial metabolismDose-dependentlyPancreatic A cellsArginine-stimulated glucagon secretionEffect of leucineAmino acidsInhibitory effectImpact of leucineSomatostatin receptor 2 antagonistsLeucineCell-intrinsicSecretory toneAcid oxidationGlucose Regulation of β-Cell KATP Channels: It Is Time for a New Model!
Merrins M, Kibbey R. Glucose Regulation of β-Cell KATP Channels: It Is Time for a New Model! Diabetes 2024, 73: 856-863. PMID: 38768366, PMCID: PMC11109790, DOI: 10.2337/dbi23-0032.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsCitationsAltmetricMeSH Keywords and ConceptsConceptsB-cell metabolismInsulin secretionEfficiency of mitochondrial ATP productionModel of glucose-stimulated insulin secretionGlucose-stimulated insulin secretionMitochondrial ATP productionNADPH productionGenetic evidenceInitial insulin secretionATP productionGlycolytic enzymesOXPHOSPyruvate kinaseATP/ADP ratioHealthy B cellsKATP channel closureB cellsDiabetes pathophysiologyGlycolysisStoichiometric yieldKATP channelsBioenergeticsATP/ADPMembrane depolarizationMetabolism
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300 George Street
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Rm 2304
New Haven, CT 06511
300 George Street
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Rm 2320
New Haven, CT 06511