Autoantibodies in recent onset type-1 diabetic patients to a Mr 60K microsomal hepatic protein: new evidence for autoantibodies to the type-2 glucosetransporter

Here we describe the presence of IgG antibodies, in the sera of patients pr esenting with insulin-dependent diabetes mellitus (IDDM), that react in Wes tern blots with a 60-kD protein (Mr 60K) from rat hepatic microsomal extrac ts. Sera from 60 IDDM patients were screened and 31.6% were positive for th e Mr 60K band. This antibody reactivity was indistinguishable in terms of b oth molecular weight and isoelectric point (pI 5.4) from that described in some patients presenting with autoimmune hepatitis who may also develop IDD M. We hypothesized that the type-2 glucose transporter (Glut-2) that is exp ressed on both hepatocytes and pancreatic beta cells could be a putative ta rget for the detected antibodies. A polyclonal antisera to rat Glut-2 used in the liver microsome Western blot identified a 60-kD band superimposable upon that evidenced by IDDM sera. Antisera to Glut-2 successfully inhibited the binding of the patient's IgGs to liver microsomes, further suggesting that the two proteins may be identical. Using protein extracts from a rat i nsulinoma cell line (RIN) transfected with the human Glut-2 cDNA, further e vidence was obtained suggesting that these IDDM IgGs are specific for the h uman Glut-2 transporter.