Human β-Cell proliferation and intracellular signaling: Part 3

Andrew F. Stewart, Mehboob A. Hussain, Adolfo García-Ocaña, Rupangi C. Vasavada, Anil Bhushan, Ernesto Bernal-Mizrachi, Rohit N. Kulkarni

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

This is the third in a series of Perspectives on intracellular signaling pathways coupled to proliferation in pancreatic β-cells. We contrast the large knowledge base in rodent β-cells with the more limited human database. With the increasing incidence of type 1 diabetes and the recognition that type 2 diabetes is also due in part to a deficiency of functioning β-cells, there is great urgency to identify therapeutic approaches to expand human β-cell numbers. Therapeutic approaches might include stem cell differentiation, transdifferentiation, or expansion of cadaver islets or residual endogenous β-cells. In these Perspectives, we focus on β-cell proliferation. Past Perspectives reviewed fundamental cell cycle regulation and its upstream regulation by insulin/IGF signaling via phosphatidylinositol-3 kinase/ mammalian target of rapamycin signaling, glucose, glycogen synthase kinase-3 and liver kinase B1, protein kinase Cz, calcium-calcineurin-nuclear factor of activated T cells, epidermal growth factor/platelet-derived growth factor family members, Wnt/β-catenin, leptin, and estrogen and progesterone. Here, we emphasize Janus kinase/signal transducers and activators of transcription, Ras/Raf/extracellular signal-related kinase, cadherins and integrins, G-protein-coupled receptors, and transforming growth factor β signaling. We hope these three Perspectives will serve to introduce these pathways to new researchers and will encourage additional investigators to focus on understanding how to harness key intracellular signaling pathways for therapeutic human β-cell regeneration for diabetes.

Original languageEnglish (US)
Pages (from-to)1872-1885
Number of pages14
JournalDiabetes
Volume64
Issue number6
DOIs
StatePublished - Jun 2015
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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  • Cite this

    Stewart, A. F., Hussain, M. A., García-Ocaña, A., Vasavada, R. C., Bhushan, A., Bernal-Mizrachi, E., & Kulkarni, R. N. (2015). Human β-Cell proliferation and intracellular signaling: Part 3. Diabetes, 64(6), 1872-1885. https://doi.org/10.2337/db14-1843