Type 1 diabetic serum interferes with pancreatic beta-cell Ca2+-handling.
The aim of this study was to clarify the frequency of patients with type 1 diabetes that have serum that increases pancreatic beta-cell cytoplasmic free Ca(2+) concentration, [Ca(2+)](i), and if such an effect is also present in serum from first-degree relatives. We also studied a possible link between the serum effect and ethnic background as well as presence of autoantibodies. Sera obtained from three different countries were investigated as follows: 82 Swedish Caucasians with newly diagnosed type 1 diabetes, 56 Americans with different duration of type 1 diabetes, 117 American first-degree relatives of type 1 diabetic patients with a mixed ethnic background and 31 Caucasian Finnish children with newly diagnosed type 1 diabetes. Changes in [Ca(2+)](i) , upon depolarization, were measured in beta-cells incubated overnight with sera from type 1 diabetic patients, first-degree relatives or healthy controls. Our data show that there is a group constituting approximately 30% of type 1 diabetic patients of different gender, age, ethnic background and duration of the disease, as well as first-degree relatives of type 1 diabetic patients, that have sera that interfere with pancreatic beta-cell Ca(2+)-handling. This effect on beta-cell [Ca(2+)](i) could not be correlated to the presence of autoantibodies. In a defined subgroup of patients with type 1 diabetes and first-degree relatives a defect Ca(2+)-handling may aggravate development of beta-cell destruction.
Dekki
N
N
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Karolinska University Hospital, L1, Stockholm, 171 76, Sweden.
Nilsson
R
R
Norgren
S
S
Rössner
S M
SM
Appelskog
I
I
Marcus
C
C
Simell
O
O
Pugliese
A
A
Alejandro
R
R
Ricordi
C
C
Berggren
P O
PO
Juntti-Berggren
L
L
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000818:Animals; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000208:ethnology / Q000235:genetics / Q000276:immunology; D005190:Family; D005260:Female; D005387:Finland; D006801:Humans; D007223:Infant; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D044967:Serum / Q000276:immunology / Q000378:metabolism*; D012737:Sex Factors; D013548:Sweden; D013997:Time Factors; D014481:United States
D001323:Autoantibodies; D002118:Calcium