To define cellular markers of the genetic heterogeneity underlying diabetes mellitus, we have examined insulin binding and insulin action in cultured skin fibroblasts from three diabetic and three unaffected individuals from a single family with a genetically defined subtype of non-insulin-dependent diabetes, maturity-onset diabetes of the young (MODY).1 Cells of two of the three MODY cell lines grew more slowly, were larger, and contained significantly more protein than did cells from their unaffected relatives. Binding of 125I-insulin was saturable and reversible, and halfmaximal displacement of tracer insulin occurred at 6 ng/ml (1 nM) unlabeled insulin in both normal and MODY cells. At physiologic concentrations of 125I-insulin (0.6 ng/ml), there was no difference in hormone binding between nondiabetic and diabetic cells when expressed as pg insulin bound per mg protein (26.0 ± 2.4 vs. 25.8 ± 2.1). When expressed as pg insulin bound per 106 cells, diabetic cells actually bound somewhat more insulin than nondiabetic cells. Insulin stimulated the transport of β-[14C]-methylaminoisobutyric acid (MeAlB) by increasing the Vmax for transport without changing the apparent Km. The insulin stimulation was half-maximal at 6 ng/ml and maximal at 100 ng/ml in both diabetic and control cells. Basal rates of transport of 0.1 mM MeAlB were the same in cells from patients and nondiabetic relatives (54 ± 7 vs. 53 ± 5 pmol · min−1 · mg protein−1); insulin stimulated a two-fold increase in transport in both. Dexamethasone (0.1 fiM) enhanced the insulin stimulation of MeAlB transport to the same extent in MODY (163 ± 23 pmol · min−1 · mg−1) and normal cells (172 ± 19). We conclude that skin fibroblasts from patients with this type of MODY are indistinguishable from cells of their unaffected relatives, with respect to insuinsulin binding and insulin stimulation of amino acid transport.
Insulin Binding and Insulin Action in Fibroblasts from Patients with Maturity-onset Diabetes of the Young
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Thomas Gelehrter, Vickie Dilworth, Beth Valka, Roderick McDonald, Elizabeth Schorry; Insulin Binding and Insulin Action in Fibroblasts from Patients with Maturity-onset Diabetes of the Young. Diabetes 1 November 1981; 30 (11): 940–946. https://doi.org/10.2337/diab.30.11.940
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