title: Preservation of Reduced Numbers of Insulin-Positive Cells in Sulfonylurea-Unresponsive KCNJ11-Related Diabetes.
abstract: The most common genetic cause of permanent neonatal diabetes mellitus is activating mutations in KCNJ11, which can usually be treated using oral sulfonylureas (SUs) instead of insulin injections, although some mutations are SU unresponsive. In this work, we provide a report of the pancreatic islet endocrine cell composition and area in a patient with an SU-unresponsive KCNJ11 mutation (p.G334D), in comparison with age-matched controls.
  
  
  
  Pancreatic autopsy tissue sections from a 2-year-old female child diagnosed with KCNJ11-related diabetes at 4 days of age and 13 age-matched controls were stained with insulin, glucagon, somatostatin, pancreatic polypeptide, and Ki67 antibodies to determine islet endocrine cell composition and area. β-cell ultrastructure was assessed by electron microscopic (EM) analysis. The patient's pancreas (sampling from head to tail) revealed insulin-positive cells in all regions. The pancreatic β-cell (insulin) area was significantly reduced compared with controls: 0.50% ± 0.04% versus 1.67% ± 0.20%, respectively (P < 0.00001). There were no significant differences in α-cell (glucagon) or δ-cell (somatostatin) area. EM analysis revealed secretory granules with a dense core typical of mature β-cells as well as granules with a lighter core characteristic of immature granules.
  
  
  
  Our results suggest that mechanisms exist that allow preservation of β-cells in the absence of insulin secretion. It remains to be determined to what extent this reduction in β-cells may be reversible.
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Siri Atma W
authors: SA
authors: Greeley
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Mark C
authors: MC
authors: Zielinski
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Ananta
authors: A
authors: Poudel
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Honggang
authors: H
authors: Ye
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Shivani
authors: S
authors: Berry
authors: Department of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Evanston Hospital, Evanston, Illinois 60201; and.
authors: Jerome B
authors: JB
authors: Taxy
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: David
authors: D
authors: Carmody
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Donald F
authors: DF
authors: Steiner
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Louis H
authors: LH
authors: Philipson
authors: Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106.
authors: Jamie R
authors: JR
authors: Wood
authors: Section of Adult and Pediatric Endocrinology, University of Chicago, Chicago, Illinois 60637.
authors: Manami
authors: M
authors: Hara
mesh_terms: D001344:Autopsy; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D016022:Case-Control Studies; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007328:Insulin / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009154:Mutation / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011379:Prognosis; D013453:Sulfonylurea Compounds / Q000494:pharmacology*; D000099161:Kcnj11 Channel
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel