title: β-Cell Deficit in Obese Type 2 Diabetes, a Minor Role of β-Cell Dedifferentiation and Degranulation.
abstract: BACKGROUND
  Type 2 diabetes is characterized by a β-cell deficit and a progressive defect in β-cell function. It has been proposed that the deficit in β-cells may be due to β-cell degranulation and transdifferentiation to other endocrine cell types.
  
  
  OBJECTIVE
  The objective of the study was to establish the potential impact of β-cell dedifferentiation and transdifferentiation on β-cell deficit in type 2 diabetes and to consider the alternative that cells with an incomplete identity may be newly forming rather than dedifferentiated.
  
  
  METHODS
  Pancreata obtained at autopsy were evaluated from 14 nondiabetic and 13 type 2 diabetic individuals, from four fetal cases, and from 10 neonatal cases.
  
  
  RESULTS
  Whereas there was a slight increase in islet endocrine cells expressing no hormone in type 2 diabetes (0.11 ± 0.03 cells/islet vs 0.03 ± 0.01 cells/islet, P < .01), the impact on the β-cell deficit would be minimal. Furthermore, we established that the deficit in β-cells per islet cannot be accounted for by an increase in other endocrine cell types. The distribution of hormone negative endocrine cells in type 2 diabetes (most abundant in cells scattered in the exocrine pancreas) mirrors that in developing (embryo and neonatal) pancreas, implying that these may represent newly forming cells.
  
  
  CONCLUSIONS
  Therefore, although we concur that in type 2 diabetes there are endocrine cells with altered cell identity, this process does not account for the deficit in β-cells in type 2 diabetes but may reflect, in part, attempted β-cell regeneration.
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Alexandra E
authors.initials: AE
authors.lastname: Butler
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Dhawan
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Hoang
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Megan
authors.initials: M
authors.lastname: Cory
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Kylie
authors.initials: K
authors.lastname: Zeng
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Helga
authors.initials: H
authors.lastname: Fritsch
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rizza
authors.affiliation: Larry L. Hillblom Islet Research Center (A.E.B., S.D., J.H., M.C., K.Z., P.C.B.), David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095-7073; Institute of Pathology (H.F.), Division of Clinical and Functional Anatomy, Medical University of Innsbruck, A-6020 Innsbruck, Austria; St Josef Hospital of the Ruhr-University Bochum (J.J.M.), 44791 Bochum, Germany; and Division of Endocrinology, Diabetes, Metabolism, and Nutrition (R.A.R.), Mayo Clinic College of Medicine, Rochester, Minnesota 55905.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Butler
mesh_terms: D000367:Age Factors; D000368:Aged; D001344:Autopsy; D015992:Body Mass Index; D054337:Cell Dedifferentiation; D015550:Cell Degranulation; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000473:pathology*; D006801:Humans; D007231:Infant, Newborn; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000473:pathology*; D010179:Pancreas / Q000473:pathology