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A constant paradox for researchers working in the field of insulin and insulin-like growth factor-I (IGF-I), is to explain how these proteins despite binding to and activating highly homologous membrane receptors and triggering similar signalling pathways, yet exert distinct physiological roles in the control of metabolism and growth. Despite extensive studies, the molecular basis for the specificity between insulin and IGF-I signaling is still poorly understood. In an attempt to reveal the gene expression profiles regulated by their divergent functions, we used Affymetrix microarrays to monitor gene expression patterns that are regulated by either insulin or IGF-I. A fully differentiated human adipocyte line, derived from the adipose tissue of a child with Simpson-Golabi-Behmel Syndrome (SGBS), was stimulated with either insulin or IGF-I. Following stimulation of the differentiated adipocytes with insulin for 24 h, we found 329 genes differentially regulated of which 215 were up-regulated and 114 were down-regulated. When SGBS adipocytes were stimulated with IGF-I, 103 genes were differentially expressed, of which 70 were up-regulated and 33 were down-regulated. Our results indicate that under the conditions used in the present study, insulin is a more potent regulator of gene expression in human adipocytes than IGF-I.