Prophylactic insulin treatment of diabetes-prone BB/OK rats by application of a sustained release insulin implant.
Normoglycemic diabetes-prone BB/OK rats aged 33, 45 or 75 days were subjected to prophylactic insulin treatment by means of a single subcutaneous application of a sustained release insulin implant. The single application of a sustained release insulin implant decreased the incidence of diabetes or delayed the onset of the disease in BB/OK rats of all treatment groups. Prophylactic insulin administration caused a transient hypoglycemic period accompanied by an inhibition of glucose stimulated insulin secretion and a decrease of the insulin content of Langerhans' islets as detectable in vitro. Compared to islets of normoglycemic controls pancreatic islets isolated from hypoglycemic BB/OK rats within 7-21 days after the insulin application at 45 days of age displayed a decreased susceptibility of the cells to complement-dependent cytotoxicity of the monoclonal islet cell surface antibody (ICSA) K14D10 but not to the cytotoxic effect of the ICSA M3aG8. The appearance of complement-dependent antibody-mediated cytotoxicity to islet cells and pancreatic exocrine cells in serum regarded as a sign of immune dysregulation in BB/OK rats seems not to be affected by insulin prophylaxis and was detectable during hypoglycemia as well as in the subsequent normoglycemic state. In conclusion, BB/OK rats of different age can be protected from diabetes by a single application of a sustained release insulin implant. Insulin and/or hypoglycemia seem to influence the expression of cell surface antigens, thus render the islets of Langerhans less vulnerable to immune cytolysis, whereas the appearance of humoral immunological abnormalites is not affected.
Schröder
Dieter
D
Institute of Pathophysiology, Ernst-Moritz-Arndt-University of Greifswald, Germany.
Ratke
Matthias
M
Bauer
Uta Christina
UC
Klöting
Ingrid
I
Ziegler
Brigitte
B
Schmidt
Siegfried
S
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D004198:Disease Susceptibility; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use*; D007332:Insulin Infusion Systems; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D005947:Glucose