• Insulin Signaling
• Type 2 Diabetes
• Atherosclerosis

• Draznin B, Miles PDG, Kruszynska Y, Olefsky JM, Friedman ME, Goalstone ML, Golovchenko I, Stjernholm R, Wall K, and Leitner JW. (2000). Hyperinsulinemia increases amounts of farnesylated p21Ras. Endocrinology 141:1310-1316.

• Goalstone ML, and Sadler SE (2000). Analysis of Farnesyl Transferase activity during hormone induced maturation of Xenopus laevis oocytes. J. Exper. Biol. 286:193-203.

• Chappell J, Golovchenko I, Wall K, Stjernholm R, Leitner JW, Goalstone ML, and Draznin B. (2000). Potentiation of Rho-A mediated LPA activity by hyperinsulinemia. J. Biol. Chem. 275:31792-31797

• Golovchenko I, Goalstone ML, Watson P, Brownlee M, and Draznin B. (2000). Hyperinsulinemia enhances transcriptional activity of NFk B induced by angiotensin II, hyperglycemia and advanced glycosylation end products in vascular smooth muscle cells. Circ. Res. 87:746-752

• Goalstone ML, Leitner JW, Berhanu P, Sharma PM, Olefsky JM, and Draznin B. (2000) Insulin signals to prenyl transferases via the Shc branch of the intracellular signaling. J. Biol. Chem. 276:12805-12812.

Reviewer:

Insulin’s effect of glucose transport into cells and the metabolic effects of glucose have been greatly studied. In contrast, the mitogenic effects of insulin have not been characterized until recently. We have discovered a novel effect of insulin action: the augmentation of cellular responses to other growth factors via insulin signaling. In particular, we have determined that insulin potentiates cellular responses to other growth factors by increasing the amounts of intracellular prenylated proteins via insulin-stimulated activation of the protein prenyltransferases.

We have been particularly interested in insulin-stimulated activation of the mitogenic effects of the prenyltransferases in vascular smooth muscle cells. We have shown that the proliferative events (e.g., increased DNA synthesis, increased transcription and shorter cell cycle) of these cells in response to other growth factors are potentiated in the presence of hyperinsulinemia.

Hyperinsulinemia is present in both Type I and Type II diabetes, and appears to be an independent risk factor for vascular disease. We are especially interested in the role that insulin plays in promoting the pathogenesis of atherosclerosis via the proliferative events of VSMC. Thus, it would be of interest to find out what cellular pathways mediate in the proliferative events of VSMC and what role they play in atherosclerosis. Therefore, by characterizing the insulin-stimulated activation of the prenyltransferases, one could determine the extent to which these enzymes are involved in the progression of this disease.

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