title: Predominance of β-cell neogenesis rather than replication in humans with an impaired glucose tolerance and newly diagnosed diabetes.
abstract: BACKGROUND
  A decrease in pancreatic β-cell mass is involved in the development of type 2 diabetes.
  
  
  OBJECTIVE
  The purpose of this study was to evaluate the β-cell mass and the incidence of β-cell neogenesis, replication, and apoptosis at both the prediabetic and diabetic stages.
  
  
  METHODS
  We conducted a cross-sectional study of pancreatic tissues obtained from 42 patients undergoing a pancreatectomy who were classified into 4 groups: normal glucose tolerance (n = 11), impaired glucose tolerance (n = 11), newly diagnosed diabetes (n = 10), and long-standing type 2 diabetes (n = 10).
  
  
  RESULTS
  The relative β-cell area decreased and the β-cell apoptosis increased during the development of diabetes. The number of single and clustered β-cells, some of which coexpressed nestin, increased in the patients with impaired glucose tolerance and newly diagnosed diabetes. The prevalence of cells positive for both insulin and glucagon or somatostatin also increased in these patients compared with those with normal glucose tolerance. These double-positive cells were mainly localized in single and clustered β-cells, rather than large islets, and were also positive for Pdx1 or Ngn3. The percentage of insulin-positive cells embedded within ducts increased in the impaired glucose tolerance group. There were no significant differences in the incidence of cells positive for both insulin and Ki67 among the groups.
  
  
  CONCLUSIONS
  These results suggest that β-cell neogenesis, rather than replication, predominates during impaired glucose tolerance and newly diagnosed diabetes in humans and may serve as a compensatory mechanism for the decreased β-cell mass.
authors.affiliation: Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yoneda
authors.forename: S
authors.initials: S
authors.lastname: Uno
authors.forename: H
authors.initials: H
authors.lastname: Iwahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Fujita
authors.forename: A
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: J
authors.initials: J
authors.lastname: Kozawa
authors.forename: K
authors.initials: K
authors.lastname: Okita
authors.forename: D
authors.initials: D
authors.lastname: Takiuchi
authors.forename: H
authors.initials: H
authors.lastname: Eguchi
authors.forename: H
authors.initials: H
authors.lastname: Nagano
authors.forename: A
authors.initials: A
authors.lastname: Imagawa
authors.forename: I
authors.initials: I
authors.lastname: Shimomura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D049109:Cell Proliferation; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D007381:Intermediate Filament Proteins / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism; D064231:Nestin; D010179:Pancreas / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D011236:Prediabetic State / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D012038:Regeneration; D015534:Trans-Activators / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D018398:Homeodomain Proteins; D007381:Intermediate Filament Proteins; D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D064231:Nestin; D015534:Trans-Activators; C577484:NES protein, human; C498695:NEUROG3 protein, human; C084010:pancreatic and duodenal homeobox 1 protein