Autoantibodies to a 64-Kilodalton Islet Cell Protein Precede the Onset of Spontaneous Diabetes in the BB Rat

Bækkeskov, Steinunn; Dyrberg, Thomas; Lernmark, Åke

doi:10.1126/science.6374896

Cited by 142 publications

(55 citation statements)

References 20 publications

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“…Similar observations have been made in the spontaneously diabetic BB rat (Table 3) which develops insulin-dependent diabetes with many similarities to that in man [45]. In some animals which later developed insulin-dependent diabetes, both ICSA and autoantibodies against an Mr 64000 component were present even at the time of weaning [46,47]. Protein II/lIlI 230aa Sig 7 D1 D2 TMCT 3'NONn a I CODI N G C DNA 32p 790bp Fig.6.…”

Section: What Is the Fl-cell Autoantigen?supporting

confidence: 74%

Molecular biology of Type 1 (insulin-dependent) diabetes mellitus

Lernmark¹

1985

Diabetologia

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Section: What Is the Fl-cell Autoantigen?supporting

confidence: 74%

Molecular biology of Type 1 (insulin-dependent) diabetes mellitus

Lernmark¹

1985

Diabetologia

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“…They were detected in selected individuals up to 8 years prior to onset [12] with high frequency at onset [15,19] and prolonged persistence after onset [48]. The 64K antibodies were also detected in sera from diabetic BB rats [49] and non-obese diabetic (NOD) mice [50] as early as the time of weaning. Thus, 64K antibodies are present early in the pathogenesis not only of human Type 1 diabetes but also in autoimmune diabetic syndromes in rodents.…”

Section: Resultsmentioning

confidence: 99%

Risk for developing Type 1 (insulin-dependent) diabetes mellitus and the presence of islet 64K antibodies

et al. 1991

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Summary. First-degree relatives of Type i (insulin-dependent) diabetic patients are at increased risk for developing clinical diabetes. The presence of islet cell or insulin autoantibodies further identifies relatives at greater risk, but not all immunologic-marker-positive relatives progress to disease. Beta-cell dysfunction, however, seems to be more prevalent than clinical Type 1 diabetes, since stable subclinical pancreatic Beta-cell dysfunction may occur. Antibodies against a Mr 64,000 (64K) islet Beta-cell protein, identified as glutamic acid decarboxylase, have been reported both at and several years prior to the clinical onset of Type i diabetes. We measured 64K antibodies in first-degree relatives with varying degrees of Beta-cell dysfunction and risk for subsequent Type i diabetes to determine whether 64K antibodies improve the predictive power of islet cell antibodies and/or insulin autoantibodies. In the Seattle Family Study first-degree relatives of Type 1 diabetic patients are followed prospectively using detailed Beta-cell function tests, insulin sensitivity, quantitative evaluation of islet cell antibodies and fluid phase assay insulin autoantibodies. 64K antibodies were measured using dog islets. Relatives were selected, based on Beta-cell function to represent individuals at high (n = 6) and low (n = 30) risk for subsequent Type 1 diabetes. The 30 low-risk individuals followed-up for 78 months, had stable Beta-cell function, and six (20%) were negative for all autoantibodies, ten (33%) were positive for insulin autoantibodies, 16 (53%) were islet cell antibody positive While six (20%) were positive for 64K antibodies. In contrast, of the six subjects with progressively declining Beta-cell function who are therefore at high risk, two of whom have already developed Type i diabetes, two (33%) were positive for insulin autoantibodies, four (67%) were islet cell antibody positive, while all six (100%) were positive for 64K antibodies. We conclude that antibodies to the Mr 64,000 islet protein correlate with progressive Beta-cell dysfunction more closely than either islet cell antibodies or insulin autoantibodies, but can sometimes be present in individuals whose Beta-cell function remains stable over several years.

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“…The first step in BB rat diabetes development is signs that the beta cells fail in function. Initially, islet autoantibodies were observed but in outbred BB rats only (Baekkeskov et al, 1984).…”

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confidence: 99%