title: α-Cells are dispensable in postnatal morphogenesis and maturation of mouse pancreatic islets.
abstract: Glucagon-producing α-cells are the second-most abundant cell type in the islet. Whereas α-cells make up less than 20% of the cells in a mature mouse islet, they occupy a much larger proportion of the pancreatic endocrine cell population during the early postnatal period, the time when morphological and functional maturation occurs to form adult islets. To determine whether α-cells have a role in postnatal islet development, a diphtheria toxin-mediated α-cell ablation mouse model was established. Rapid and persistent depletion of α-cells was achieved by daily injection of the toxin for 2 wk starting at postnatal day 1 (P1). Total pancreatic glucagon content in the α-cell-ablated mice was undetectable at P14 and still less than 0.3% of that of the control mice at 4 mo of age. Histological analyses revealed that formation of spherical islets occurred normally, and the islet size distribution was not changed despite the near-total lack of α-cells. Furthermore, there were no differences in expression of β-cell maturation marker proteins, including urocortin 3 and glucose transporter 2, in the α-cell-ablated islets at P14. Mice lacking α-cells grew normally and appeared healthy. Both glucose and insulin tolerance tests demonstrated that the α-cell-ablated mice had normal glucose homeostasis. These results indicate that α-cells do not play a critical role in postnatal islet morphogenesis or functional maturation of β-cells.
authors: Division of Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
authors: Chiyo
authors: C
authors: Shiota
authors: Krishna
authors: K
authors: Prasadan
authors: Ping
authors: P
authors: Guo
authors: Yousef
authors: Y
authors: El-Gohary
authors: John
authors: J
authors: Wiersch
authors: Xiangwei
authors: X
authors: Xiao
authors: Farzad
authors: F
authors: Esni
authors: George K
authors: GK
authors: Gittes
mesh_terms: D055011:Ablation Techniques; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000378:metabolism; D005091:Exons; D005260:Female; D005934:Glucagon / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050416:Glucagon-Secreting Cells / Q000502:physiology*; D051273:Glucose Transporter Type 2 / Q000378:metabolism; D006984:Hypertrophy; D007003:Hypoglycemia / Q000209:etiology; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism; D007515:Islets of Langerhans / Q000166:cytology / Q000254:growth & development* / Q000601:surgery; D008164:Luminescent Proteins / Q000737:chemistry / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000473:pathology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D054832:Urocortins / Q000378:metabolism
chemical_list: D015415:Biomarkers; D051273:Glucose Transporter Type 2; D008164:Luminescent Proteins; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; C495682:Slc2a2 protein, mouse; D054832:Urocortins; C549823:urocortin 3 protein, mouse; D005934:Glucagon
keywords: cell ablation; glucagon; islets of Langerhans; pancreatic islet development; pancreatic α-cell