APA
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Ouaamari, A. E., Dirice, E., Gedeon, N., Hu, J., Zhou, J., Shirakawa, J., … Kulkarni, R. (2016). SerpinB1 Promotes Pancreatic β-Cell Proliferation. Cell Metabolism.
Chicago/Turabian
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Ouaamari, Abdelfattah El, E. Dirice, N. Gedeon, Jiang Hu, Jianying Zhou, J. Shirakawa, Lifei Hou, et al. “SerpinB1 Promotes Pancreatic β-Cell Proliferation.” Cell Metabolism (2016).
MLA
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Ouaamari, Abdelfattah El, et al. “SerpinB1 Promotes Pancreatic β-Cell Proliferation.” Cell Metabolism, 2016.
BibTeX Click to copy
@article{abdelfattah2016a,
title = {SerpinB1 Promotes Pancreatic β-Cell Proliferation},
year = {2016},
journal = {Cell Metabolism},
author = {Ouaamari, Abdelfattah El and Dirice, E. and Gedeon, N. and Hu, Jiang and Zhou, Jianying and Shirakawa, J. and Hou, Lifei and Goodman, Jessica and Karampelias, Christos and Qiang, G. and Boucher, J. and Martinez, Rachael and Gritsenko, M. and Jesus, Dario F. De and Kahraman, S. and Bhatt, S. and Smith, Richard D. and Beer, H. and Jungtrakoon, Prapaporn and Gong, Y. and Goldfine, A. and Liew, C. and Doria, A. and Andersson, Olov and Qian, W. and Remold-O’Donnell, E. and Kulkarni, R.}
}
Summary Although compensatory islet hyperplasia in response to insulin resistance is a recognized feature in diabetes, the factor(s) that promote β-cell proliferation have been elusive. We previously reported that the liver is a source for such factors in the liver insulin receptor knockout (LIRKO) mouse, an insulin resistance model which manifests islet hyperplasia. Using proteomics we show that serpinB1, a protease inhibitor, which is abundant in the hepatocyte secretome and sera derived from LIRKO mice, is the liver-derived secretory protein that regulates β-cell proliferation in humans, mice and zebrafish. Small molecule compounds, that partially mimic serpinB1 effects of inhibiting elastase activity, enhanced proliferation of β-cells, and mice lacking serpinB1 exhibit attenuated β-cell compensation in response to insulin resistance. Finally, SerpinB1-treatment of islets modulated proteins in growth/survival pathways. Together, these data implicate serpinB1 as an endogenous protein that can potentially be harnessed to enhance functional β-cell mass in patients with diabetes.