title: Human islets contain four distinct subtypes of β cells.
abstract: Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant.
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Craig
authors.identifier: 0000-0001-5129-5628
authors.initials: C
authors.lastname: Dorrell
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity, and Metabolism; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Schug
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Pamela S
authors.initials: PS
authors.lastname: Canaday
authors.affiliation: Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Holger A
authors.initials: HA
authors.lastname: Russ
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Branden D
authors.initials: BD
authors.lastname: Tarlow
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Maria T
authors.initials: MT
authors.lastname: Grompe
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Horton
authors.affiliation: Diabetes Center, Department of Medicine, University of California San Francisco, San Francisco, California 94143, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Hebrok
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Philip R
authors.initials: PR
authors.lastname: Streeter
authors.affiliation: Department of Genetics and Institute for Diabetes, Obesity, and Metabolism; University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Klaus H
authors.initials: KH
authors.lastname: Kaestner
authors.affiliation: Oregon Stem Cell Center, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
authors.forename: Markus
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans; D008297:Male; D008875:Middle Aged; D012799:Sialyltransferases / Q000378:metabolism*; D060245:Tetraspanin 29 / Q000378:metabolism*; D055815:Young Adult
chemical_list: D006442:Glycated Hemoglobin; D012799:Sialyltransferases; D060245:Tetraspanin 29; C554869:CD9 protein, human; C517652:hemoglobin A1c protein, human; C043662:alpha-N-acetylneuraminate alpha-2,8-sialyltransferase