title: Human β-cell proliferation and intracellular signaling part 2: still driving in the dark without a road map.
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 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.
authors.affiliation: Division of Metabolism, Endocrinology, and Diabetes, University of Michigan, and U.S. Department of Veterans Affairs Ann Arbor Healthcare System, Ann Arbor, MI.
authors.forename: Ernesto
authors.initials: E
authors.lastname: Bernal-Mizrachi
authors.forename: Rohit N
authors.initials: RN
authors.lastname: Kulkarni
authors.forename: Donald K
authors.initials: DK
authors.lastname: Scott
authors.forename: Franck
authors.initials: F
authors.lastname: Mauvais-Jarvis
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Stewart
authors.forename: Adolfo
authors.initials: A
authors.lastname: Garcia-Ocaña
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases / Q000502:physiology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000502:physiology; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000517:prevention & control; D066246:ErbB Receptors / Q000502:physiology; D004967:Estrogens / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000502:physiology*; D020738:Leptin / Q000502:physiology; D050778:NFATC Transcription Factors / Q000502:physiology; D011374:Progesterone / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D060449:Wnt Signaling Pathway / Q000502:physiology
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004967:Estrogens; D020738:Leptin; C116385:MLXIPL protein, human; D050778:NFATC Transcription Factors; D011374:Progesterone; D066246:ErbB Receptors; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose