Human β-Cell Proliferation and Intracellular Signaling Part 2: Still Driving in the Dark Without a Road Map
- Ernesto Bernal-Mizrachi1⇑,
- Rohit N. Kulkarni2,3,
- Donald K. Scott4,
- Franck Mauvais-Jarvis5,
- Andrew F. Stewart4 and
- Adolfo Garcia-Ocaña4,6⇑
- 1Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, and U.S. Department of Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI
- 2Islet Cell Biology and Regenerative Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, MA
- 3Department of Medicine, Harvard Medical School, Boston, MA
- 4Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, NY
- 5Division of Endocrinology and Metabolism, Tulane University School of Medicine and Health Sciences Center, New Orleans, LA
- 6Mindich Child Health and Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY
- Corresponding authors: Ernesto Bernal-Mizrachi, , and Adolfo Garcia-Ocaña, .
Enhancing β-cell proliferation is a major goal for type 1 and type 2 diabetes research. Unraveling the network of β-cell intracellular signaling pathways that promote β-cell replication can provide the tools to address this important task. In a previous Perspectives in Diabetes article, we discussed what was known regarding several important intracellular signaling pathways in rodent β-cells, including the insulin receptor substrate/phosphatidylinositol-3 kinase/Akt (IRS-PI3K-Akt) pathways, glycogen synthase kinase-3 (GSK3) and mammalian target of rapamycin (mTOR) S6 kinase pathways, protein kinase Cζ (PKCζ) pathways, and their downstream cell-cycle molecular targets, and contrasted that ample knowledge to the small amount of complementary data on human β-cell intracellular signaling pathways. In this Perspectives, we summarize additional important information on signaling pathways activated by nutrients, such as glucose; growth factors, such as epidermal growth factor, platelet-derived growth factor, and Wnt; and hormones, such as leptin, estrogen, and progesterone, that are linked to rodent and human β-cell proliferation. With these two Perspectives, we attempt to construct a brief summary of knowledge for β-cell researchers on mitogenic signaling pathways and to emphasize how little is known regarding intracellular events linked to human β-cell replication. This is a critical aspect in the long-term goal of expanding human β-cells for the prevention and/or cure of type 1 and type 2 diabetes.
- Received July 24, 2013.
- Accepted November 20, 2013.
- © 2014 by the American Diabetes Association.
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