The effects of sera obtained from children with insulin-dependent diabetes mellitus on cultivated islet cells: cytotoxicity and insulin release.
Sera were obtained from 24 patients with newly-diagnosed insulin-dependent diabetes mellitus (IDDM) and 14 children with a high risk of diabetes. The influence of the decomplementated sera on basal and stimulated insulin secretion was studied in a mixed culture of newborn rat islet cells. In addition, complement-dependent antibody-mediated cytotoxicity (C'AMC) was measured by 51Cr-release from pre-labelled islet cells. Incubation of the islet cells with sera from ten IDDM patients did not affect the basal insulin release. Sera from other children with IDDM (n = 14) either significantly increased (n = 7) or inhibited (n = 7) basal IRI secretion was compared with the sera of control donors. Nearly half of the sera from the high-risk children was found to be insulin-stimulating. Preincubation of islet cells with sera from IDDM children caused a significant decrease of insulin response to 16.5 mM glucose plus 5 mM theophylline (P less than 0.001). Sera from the high-risk children did influence the response of pancreatic cells to secretagogues. C'AMC was found in 45% of the patients with IDDM and in 33% of the high-risk children, however, there was no correlation between C'AMC and serum effect upon basal insulin secretion. These results suggest the presence of B-cytotropic factors in serum from children with IDDM or with a risk of diabetes. Opposite effects of different sera on insulin secretion may reflect the variety of pathogenetic mechanisms involved in islet cell destruction.
Sadovnikova
N V
NV
Institute for Experimental Endocrinology and Hormone Chemistry, Academy of Medical Sciences of the USSR, Moscow.
Pankov
Y A
YA
Fedotov
V P
VP
Czernushkina
A V
AV
Zhukovsky
M A
MA
Shcherbacheva
L N
LN
D000293:Adolescent; D000917:Antibody Formation; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001798:Blood Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003470:Culture Media / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male
D001798:Blood Proteins; D003470:Culture Media; D007328:Insulin