Loss of cholinergic potentiating responsiveness in mouse islets transplanted to the kidney.
Pancreatic islets from BALB/c mice were transplanted to the kidney of syngenic hosts. After 1-40 weeks, the grafts were removed, perifused in vitro, and extracted. Fresh islets were similarly examined. The graft insulin content fell by 70% in 1 week and remained low throughout the observation period. In contrast, rates of basal or glucose-stimulated insulin release were not much, if at all, decreased. In fresh islets and grafts removed after 3 or 28 weeks, 2 consecutive pulses of glucose stimulation, 20-25 min long and separated by 20 min at basal glucose concentration (2 or 2.8 mmol/L), elicited the same insulin secretory response. When 10 mumol/L acetylcholine and 10 mumol/L eserine were present during the second pulse, the glucose-stimulated insulin release from fresh islets was potentiated as much as 11-fold. This potentiation was reduced by one half during the first week of transplantation, and subsequently by 80-90%. It is concluded that vagal deprivation rapidly induces a state of persistent cholinergic refractoriness in transplanted beta-cells, despite morphological signs of autonomic reinnervation of the grafts.
Shi
C L
CL
Department of Histology and Cell Biology, Umeå University, Sweden.
Täljedal
I B
IB
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D046508:Culture Techniques; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D016381:Islets of Langerhans Transplantation; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010830:Physostigmine / Q000494:pharmacology; D013997:Time Factors; D014183:Transplantation, Heterologous; D014185:Transplantation, Isogeneic
D007328:Insulin; D010830:Physostigmine; D005947:Glucose; D000109:Acetylcholine