Insulin resistance • tyrosine kinase and phosphatase • glucose metabolism • diabetes complications • oxidative stress
My first research focus investigates the mechanisms by which cells do not respond normally to insulin in people with diabetes, and my second focus is on how high glucose causes kidney disease. My laboratory has identified new proteins and signaling pathways that will help lead to new treatments to prevent these serious complications, leading to better health and longer life for people with diabetes. More recently I have studied glucose toxicity as it relates to both insulin action and the complications of diabetes, in particular, diabetic nephropathy.
Combined Hyperglycemia- and Hyperinsulinemia-Induced Insulin Resistance in Adipocytes Is Associated with Dual Signaling Defects Mediated by PKC-ζ. Lu H, Bogdanovic E, Yu Z, Cho C, Liu L, Ho K, Guo J, Yeung LSN, Lehmann R, Hundal HS, Giacca A, Fantus IG. Endocrinology. 2018 Apr 1;159(4):1658-1677. doi: 10.1210/en.2017-00312.
The bradykinin-cGMP-PKG pathway augments insulin sensitivity via upregulation of MAPK phosphatase-5 and inhibition of JNK. Frigolet ME, Thomas G, Beard K, Lu H, Liu L, Fantus IG. Am J Physiol Endocrinol Metab. 2017 Sep 1;313(3):E321-E334. doi: 10.1152/ajpendo.00298.2016. Epub 2017 Jul 5.
Thioredoxin-Interacting Protein Deficiency Protects against Diabetic Nephropathy. Shah A, Xia L, Masson EA, Gui C, Momen A, Shikatani EA, Husain M, Quaggin S, John R, Fantus IG. J Am Soc Nephrol. 2015 Dec;26(12):2963-77. doi: 10.1681/ASN.2014050528. Epub 2015 Apr 8.
Inhibition of Src kinase blocks high glucose-induced EGFR transactivation and collagen synthesis in mesangial cells and prevents diabetic nephropathy in mice. Taniguchi K, Xia L, Goldberg HJ, Lee KW, Shah A, Stavar L, Masson EA, Momen A, Shikatani EA, John R, Husain M, Fantus IG. Diabetes. 2013 Nov;62(11):3874-86. doi: 10.2337/db12-1010. Epub 2013 Aug 13.
Thioredoxin-interacting protein mediates high glucose-induced reactive oxygen species generation by mitochondria and the NADPH oxidase, Nox4, in mesangial cells. Shah A, Xia L, Goldberg H, Lee KW, Quaggin SE, Fantus IG. J Biol Chem. 2013 Mar 8;288(10):6835-48. doi: 10.1074/jbc.M112.419101. Epub 2013 Jan 17.