WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability

Brian P Boerner, Nicholas M. George, Shakeel U R Mir, Nora E Sarvetnick

Research output: Contribution to journalComment/debate

6 Citations (Scopus)

Abstract

Agents that stimulate human pancreatic beta cell proliferation are needed to improve diabetes mellitus treatment. Recently, a small molecule, WS6, was observed to stimulate human beta cell proliferation. However, little is known about its other effects on human islets. To better understand the role of WS6 as a possible beta cell regenerative therapy, we carried out in-depth phenotypic analysis of WS6-treated human islets, exploring its effects on non-beta cell proliferation, beta cell differentiation, and islet cell viability. WS6 not only stimulated beta cell proliferation in cultured human islets (in agreement with previous reports), but also human alpha cell proliferation, indicating that WS6 is not a beta cell-specific mitogen. WS6 did not change the proportion of insulin-positive beta cells or the expression of beta cell-specific transcription factors, suggesting that WS6 does not alter beta cell differentiation, and WS6 had no effect on human islet cell apoptosis or viability. In conclusion, WS6 stimulates proliferation of both human beta and alpha cells while maintaining cellular viability and the beta cell differentiated phenotype. These findings expand the literature on WS6 and support the suggestion that WS6 may help increase human islet mass needed for successful treatment of diabetes.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalEndocrine Journal
Volume62
Issue number4
DOIs
StatePublished - Jan 1 2015

Fingerprint

Cell Proliferation
Islets of Langerhans
Cell Differentiation
Cell Survival
Insulin-Secreting Cells
Cell- and Tissue-Based Therapy
Mitogens
Diabetes Mellitus
Transcription Factors
Insulin
Apoptosis
Phenotype
Therapeutics

Keywords

  • Alpha cell
  • Differentiation
  • Human islet

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

WS6 induces both alpha and beta cell proliferation without affecting differentiation or viability. / Boerner, Brian P; George, Nicholas M.; Mir, Shakeel U R; Sarvetnick, Nora E.

In: Endocrine Journal, Vol. 62, No. 4, 01.01.2015, p. 379-386.

Research output: Contribution to journalComment/debate

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