The toxic effects of serum from patients with type 1 diabetes mellitus on mouse neuroblastoma cells: a new mechanism for development of diabetic autonomic neuropathy.
The pathogenesis of diabetic neuropathy is incompletely understood. The possibility that humoral neurotoxic factors contribute as a cause of diabetic neuropathy was tested by application of serum from patients with Type 1 and Type 2 diabetes to mouse neuroblastoma cells, which have the characteristics of adrenergic neurons in culture. Serum from patients with Type 1 diabetes and somatic neuropathy significantly inhibited both proliferation and differentiation of neuroblastoma cells, while serum from patients with Type 1 diabetes but no symptoms of neuropathy and patients with Type 2 diabetes and neuropathy had no effect on proliferation, and serum from Type 2 patients only marginally inhibited differentiation. The effects of Type 1 diabetic serum could be reversed by pre-absorption of the serum to neuroblastoma cells, and were independent of glucose levels. Immunoglobulins precipitated from the sera mimicked the effects of whole sera. These results suggest that Type 1 diabetes mellitus causes a change in serum composition, possibly related to autoimmunity, that is capable of contributing to adrenergic autonomic neuropathy in diabetic patients.
Pittenger
G L
GL
Department of Internal Medicine, Eastern Virginia Medical School, Norfolk 23510.
Liu
D
D
Vinik
A I
AI
D000328:Adult; D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000097:blood / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009447:Neuroblastoma / Q000473:pathology*; D014407:Tumor Cells, Cultured