Human β-cell proliferation and intracellular signaling part 2: Still driving in the dark without a road map

Ernesto Bernal-Mizrachi, Rohit N. Kulkarni, Donald K. Scott, Franck Mauvais-Jarvis, Andrew F. Stewart, Adolfo Garcia-Ocaña

Research output: Contribution to journalReview article

107 Scopus citations

Abstract

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 Cz (PKCz) 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.

Original languageEnglish (US)
Pages (from-to)819-831
Number of pages13
JournalDiabetes
Volume63
Issue number3
DOIs
StatePublished - Mar 1 2014
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Bernal-Mizrachi, E., Kulkarni, R. N., Scott, D. K., Mauvais-Jarvis, F., Stewart, A. F., & Garcia-Ocaña, A. (2014). Human β-cell proliferation and intracellular signaling part 2: Still driving in the dark without a road map. Diabetes, 63(3), 819-831. https://doi.org/10.2337/db13-1146