Insulin binding and activation of glycogen synthase in fibroblasts from Type 1 (insulin-dependent) diabetic patients.
125I-Insulin binding and insulin stimulation of glycogen synthase were examined in fibroblasts cultured from nine Type 1 (insulin-dependent) diabetic patients with age of onset of less than 42 years. In all cases specific insulin binding was qualitatively and quantitatively normal. Total 125I-insulin binding was elevated in cells from three patients with early onset diabetes (two with onset before age 1 year) due to an increase in 'non-specific' binding. When the ability of insulin to stimulate the conversion of the glucose-6-phosphate dependent to the glucose-6-phosphate independent form of glycogen synthase was measured, all cell lines responded, albeit to differing degrees. In general, the response of cells from diabetic donors was more variable than that of control fibroblasts. A slightly lower level of cellular glycogen was evident in the cells of the diabetic patients, and this was mirrored in slightly higher levels of the independent form of the enzyme. The average maximal level of the independent form of the enzyme also was higher in the diabetic patients' cells. Fibroblasts from one of the patients with very early onset diabetes had glycogen synthase levels that were markedly lower than in any other cell line examined. In summary, fibroblasts cultured from Type 1 diabetic patients do not show major defects in either insulin binding or action. A suggestion of subtle differences in the cells from the diabetic patients, particularly those with very early onset, is evident, however. Whether these are secondary to some primary genetic defect or represent some selection during culture remains to be determined.
D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D006006:Glycogen Synthase; D011972:Receptor, Insulin