Insulin antibody production in guinea pigs is accompanied by disturbances in pancreatic islet morphology and glucagon secretion.
Long term immunization of seven guniea pigs with crystalline porcine insulin in Freund's adjuvant resulted in the production of high titres of insulin antibodies. With the exception of one guniea pig which became hyperglycaemic by 10 weeks, normoglycaemia was maintained. After 42 weeks, the guinea pigs were killed and examined with regard to islet morphology and glucagon secretion. Immunocytochemical staining revealed an increase in the relative A-cell volume and a decrease in the relative B-cell volume. This was accompanied by a cellular rearrangement with A-cells centrally and B-cells peripherally. The islets of the hyperglycaemic guinea pig were enlarged and contained pyknotic cells with a few well-stained A-cells. Short term culture of normal guinea pig islets in the presence of serum from this animal did not lead to structural change. No evidence of insulitis or islet fibrosis was observed in any of the guinea pigs. Incubation of islets from the immunized animals in vitro revealed that the normal suppression of glucagon secretion by glucose was absent. Despite a degree of cross-reaction between antibodies and guinea pig insulin, as judged from immunocytochemical staining of guinea pig islets, there was no relationship between antibody titre and the degree of the morphological or functional disturbances. Although abnormal glucagon secretion can be partly attributed to disturbances in islet architecture, the exact mechanism remains to be elucidated.
D000818:Animals; D000917:Antibody Formation; D001786:Blood Glucose / Q000032:analysis; D005934:Glucagon / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006168:Guinea Pigs; D007330:Insulin Antibodies / Q000096:biosynthesis*; D007515:Islets of Langerhans / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008297:Male
D001786:Blood Glucose; D007330:Insulin Antibodies; D005934:Glucagon; D005947:Glucose