title: β-Cell Glucose Sensitivity Is Linked to Insulin/Glucagon Bihormonal Cells in Nondiabetic Humans.
abstract: BACKGROUND
  Insulin resistance impacts virtually all tissues, including pancreatic β cells. Individuals with insulin resistance, but without diabetes, exhibit an increased islet size because of an elevated number of both β and α cells. Neogenesis from duct cells and transdifferentiation of α cells have been postulated to contribute to the β-cell compensatory response to insulin resistance.
  
  
  OBJECTIVE
  Our objective was to explore parameters that could potentially predict altered islet morphology.
  
  
  METHODS
  We investigated 16 nondiabetic subjects by a 2-hour hyperglycemic clamp to evaluate β-cell secretory function. We analyzed pancreas samples obtained during pancreatoduodenectomy in the same patients to examine glucagon and insulin double+ cells to assess islet morphology.
  
  
  RESULTS
  Among all the functional in vivo parameters of insulin secretion that were explored (basal, first phase and total secretion, glucose sensitivity, arginine-stimulated insulin secretion), β-cell glucose sensitivity was unique in exhibiting a significant correlation with both islet size and α-β double+ islet cells.
  
  
  CONCLUSIONS
  Our data suggest that poor β-cell glucose sensitivity is linked to islet transdifferentiation, possibly from α cells to β cells, in an attempt to cope with higher demands for insulin secretion. Understanding the mechanism(s) that underlies the adaptive response of the islet cells to insulin resistance is a potential approach to design tools to enhance functional β-cell mass for diabetes therapy.
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Teresa
authors.initials: T
authors.lastname: Mezza
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Gian P
authors.initials: GP
authors.lastname: Sorice
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Conte
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Vinsin A
authors.initials: VA
authors.lastname: Sun
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Chiara M A
authors.initials: CM
authors.lastname: Cefalo
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Moffa
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Pontecorvi
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.affiliation: Endo-Metabolic Diseases Unit (T.M., G.P.S., C.C., V.A.S., C.M.A.C., S.M., A.P., A. G.), Università Cattolica del Sacro Cuore, Rome, Italy; Islet Cell & Regenerative Biology (T.M., R.H.K.), Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215; Institute of Neuroscience (A.M.), National Research Council, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Giaccari
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D006946:Hyperinsulinism / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D007515:Islets of Langerhans / Q000033:anatomy & histology / Q000166:cytology; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism; D010186:Pancreatic Function Tests; D016577:Pancreaticoduodenectomy
chemical_list: D007328:Insulin; D005934:Glucagon; D005947:Glucose