In vivo infection of mice with Coxsackie B4 virus induces long-term functional changes in pancreatic islets with minimal alteration in blood glucose.
The long-term effects of Coxsackie B4 (CB4) infection of mice on pancreatic islet function were investigated. Mice were inoculated with various strains of CB4 virus and 2, 3 and 6 months later islet insulin synthesis and release from isolated islets were measured. Insulin release at basal glucose concentration (2 mmol l-1) was higher in islets from mice inoculated with pancreas-adapted CB4 strains than in control islets or those from mice inoculated with tissue culture-adapted CB4. Thus, two strains of pancreas-adapted virus (P11 and P12) increased basal insulin release by 72% compared with control islets (p less than 0.05) 1 month after inoculation. Another strain (P13) increased insulin release by 421% at 3 months post-inoculation (p less than 0.01) and by 192% at 6 months (p less than 0.05) compared with control islets. The rate of total protein synthesis in islets from P11-inoculated mice 1 month later was 61% lower than in control islets at basal glucose levels (p less than 0.001), and was 25% lower at 20 mmol l-1 glucose (p less than 0.01). There were no significant changes in protein synthesis in islets from infected mice at 3 or 6 months. The abnormal insulin release occurred with minimal changes in random blood glucose concentrations. Histologically the islets were unchanged and there were no detectable islet cell antibodies. These results show that CB4 infection may lead to a persistent metabolic dysfunction in islets with minimal changes in blood glucose levels.
Szopa
T M
TM
Department of Biochemistry, London Hospital Medical College, UK.
Dronfield
D M
DM
Ward
T
T
Taylor
K W
KW
D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism*; D003384:Coxsackievirus Infections / Q000097:blood / Q000503:physiopathology*; D029822:Enterovirus B, Human; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D012016:Reference Values
D001323:Autoantibodies; D001786:Blood Glucose; D007328:Insulin