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 journalArticle

101 Citations (Scopus)

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 2014
Externally publishedYes

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Cell Proliferation
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Rodentia
Phosphatidylinositol 3-Kinase
Ribosomal Protein S6 Kinases
Glycogen Synthase Kinase 3
Platelet-Derived Growth Factor
Insulin Receptor
Sirolimus
Leptin
Epidermal Growth Factor
Protein Kinases
Progesterone
Intercellular Signaling Peptides and Proteins
Cell Cycle
Estrogens
Research Personnel
Hormones
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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

Human β-cell proliferation and intracellular signaling part 2 : Still driving in the dark without a road map. / Bernal Mizrachi, Ernesto; Kulkarni, Rohit N.; Scott, Donald K.; Mauvais-Jarvis, Franck; Stewart, Andrew F.; Garcia-Ocaña, Adolfo.

In: Diabetes, Vol. 63, No. 3, 03.2014, p. 819-831.

Research output: Contribution to journalArticle

Bernal Mizrachi, E, Kulkarni, RN, Scott, DK, Mauvais-Jarvis, F, Stewart, AF & Garcia-Ocaña, A 2014, 'Human β-cell proliferation and intracellular signaling part 2: Still driving in the dark without a road map', Diabetes, vol. 63, no. 3, pp. 819-831. https://doi.org/10.2337/db13-1146
Bernal Mizrachi, Ernesto ; Kulkarni, Rohit N. ; Scott, Donald K. ; Mauvais-Jarvis, Franck ; Stewart, Andrew F. ; Garcia-Ocaña, Adolfo. / Human β-cell proliferation and intracellular signaling part 2 : Still driving in the dark without a road map. In: Diabetes. 2014 ; Vol. 63, No. 3. pp. 819-831.
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