title: Impaired glucose tolerance in mice lacking cellular prion protein.
abstract: OBJECTIVE
  We previously demonstrated that the expression of cellular prion protein (PrPC) in islet [beta]-cells is suppressed in hyperglycemic rats suggesting a major role for PrPC in blood glucose regulation. To further characterize the function of PrPC in glucose homeostasis, we studied glucoregulation in PrPC knockout (PrPC KO) mice.
  
  
  METHODS
  Glucose tolerance, insulin secretion, and insulin sensitivity were analyzed to assess glucoregulation in Zrch I PrPC KO and the C57BL/6 (control) mice. Immunohistochemistry and morphometry were used to measure [beta]-cell mass.
  
  
  RESULTS
  Male PrPC KO mice had significantly increased blood glucose concentration 60, 120, and 180 minutes after intraperitoneal injection of glucose compared with C57BL/6 mice. Female PrPC KO mice showed a less pronounced phenotype of glucose intolerance. Evaluation of [beta]-cell mass, insulin and proinsulin deficiency, and insulin resistance in male mice revealed essentially no difference between PrPC KO and control mice. The only exception was an increase in serum insulin concentration in male PrPC KO mice 5 minutes after glucose injection.
  
  
  CONCLUSIONS
  This report is the first to show that PrPC in [beta]-cells is involved in glucoregulation. A further understanding of the role of PrPC in regulating [beta]-cell function will provide valuable insight into the mechanisms of blood glucose regulation.
authors.affiliation: Chronic Disease Program, Institute for Clinical Diabetology, German Diabetes Centre, Du¨sseldorf, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000378:metabolism* / Q000473:pathology*; D006706:Homeostasis; D006943:Hyperglycemia / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D018621:PrPC Proteins / Q000235:genetics / Q000378:metabolism*; D011384:Proinsulin / Q000172:deficiency; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D007328:Insulin; D018621:PrPC Proteins; D011384:Proinsulin