Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2010 Feb;15(1):79-85.
doi: 10.1097/MOT.0b013e3283344932.

Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis

Kirstine Juhl  1 , Susan Bonner-Weir, Arun Sharma
Affiliations
Review

Regenerating pancreatic beta-cells: plasticity of adult pancreatic cells and the feasibility of in-vivo neogenesis

Kirstine Juhl et al. Curr Opin Organ Transplant. 2010 Feb.

Abstract

Purpose of review: Diabetes results from inadequate functional mass of pancreatic beta-cells and therefore replenishing with new glucose-responsive beta-cells is an important therapeutic option. In addition to replication of pre-existing beta-cells, new beta-cells can be produced from differentiated adult cells using in-vitro or in-vivo approaches. This review will summarize recent advances in in-vivo generation of beta-cells from cells that are not beta-cells (neogenesis) and discuss ways to overcome the limitations of this process.

Recent findings: Multiple groups have shown that adult pancreatic ducts, acinar and even endocrine cells exhibit cellular plasticity and can differentiate into beta-cells in vivo. Several different approaches, including misexpression of transcription factors and tissue injury, have induced neogenesis of insulin-expressing cells in vivo and ameliorated diabetes.

Summary: Recent breakthroughs demonstrating cellular plasticity of adult pancreatic cells to form new beta-cells are a positive first step towards developing in-vivo regeneration-based therapy for diabetes. Currently, neogenesis processes are inefficient and do not generate sufficient amounts of beta-cells required to normalize hyperglycemia. However, an improved understanding of mechanisms regulating neogenesis of beta-cells from adult pancreatic cells and of their maturation into functional glucose-responsive beta-cells can make therapies based on in-vivo regeneration a reality.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic showing different cell sources that under in vitro or in vivo differentiation conditions transdifferentiate or dedifferentiate/redifferentiate into insulin-producing cells. Numbers in parenthesis refer to reference numbers.
See this image and copyright information in PMC

References

    1. Bonner-Weir S, Inada A, Yatoh S, et al. Transdifferentiation of pancreatic ductal cells to endocrine beta-cells. Biochem Soc Trans. 2008 Jun;36(Pt 3):353–6. - PubMed
    1. Zhou Q, Brown J, Kanarek A, et al. In vivo reprogramming of adult pancreatic exocrine cells to beta-cells. Nature. 2008 Oct 2;455(7213):627–32. - PMC - PubMed

    2. Paper provides evidence for reprogramming of adult pancreatic cells by demonstrating that in vivo misexpression of Ngn3, Pdx1 and MafA in adult acinar cells converts them to insulin-producing cells.

    1. Collombat P, Xu X, Ravassard P, et al. The Ectopic Expression of Pax4 in the Mouse Pancreas Converts Progenitor Cells into [alpha] and Subsequently [beta] Cells. Cell. 2009;138(3):449–62. - PMC - PubMed

    2. Authors provide genetic evidence that Pax4 induced in adult glucagon-expressing cells transdifferentiate them to β-cells. Furthermore, hypoglycemic condition triggers neogenesis of α-cells that upon expression of Pax4 transdifferentiate into β-cells.

    1. Xu X, D'Hoker J, Stange G, et al. Beta cells can be generated from endogenous progenitors in injured adult mouse pancreas. Cell. 2008 Jan 25;132(2):197–207. - PubMed

    2. Manuscript provides evidence for in vivo neognesis of β-cells. This study demonstrates induction of Ngn3-expressing cells in adults upon ductal ligation and that the neogenesis of b-cells depends on the expression of Ngn3.

    1. Inada A, Nienaber C, Katsuta H, et al. Carbonic anhydrase II-positive pancreatic cells are progenitors for both endocrine and exocrine pancreas after birth. Proc Natl Acad Sci U S A. 2008 Dec 16;105(50):19915–9. - PMC - PubMed

    2. Paper shows genetic lineage tracing evidence that newly formed endocrine cells are derived from CAII expressing duct cells both in neonatal stage and in adult pancreas following duct ligation.

Publication types

MeSH terms

Substances