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Wnt Signaling in Pancreatic Islets

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Islets of Langerhans

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Abstract

The Wnt signaling pathway is critically important not only for stem cell amplification, but also for the differentiation and migration and for organogenesis and the development of the body plan. β-catenin/TCF7L2-dependent Wnt signaling (the canonical pathway) is involved in pancreas development, islet function, and insulin production and secretion. The glucoincretin hormone glucagon-like peptide-1 and the chemokine stromal cell-derived factor-1 modulate canonical Wnt signaling in β cells which is obligatory for their mitogenic and cytoprotective actions.

Genome-wide association studies have uncovered approximately 90 gene loci that confer susceptibility for the development of type 2 diabetes (Marchetti P, Syed F, Suleiman M, Bugliani M, Marselli L, Islets 4:323–332, 2012). The majority of these diabetes risk alleles encode proteins that are implicated in islet growth and functioning (Marchetti P, Syed F, Suleiman M, Bugliani M, Marselli L, Islets 4:323–332, 2012, Ahlqvist E, Ahluwalia TS, Groop L, Clin Chem 57:241–254, 2011). At least 20 of the type 2 diabetes genes that affect islet functions are either components of or known target genes for Wnt signaling. The transcription factor TCF7L2 is particularly strongly associated with risk for diabetes and appears to be fundamentally important in both canonical Wnt signaling and β cell functioning. Experimental loss of TCF7L2 function in islets and polymorphisms in TCF7L2 alleles in humans impair glucose-stimulated insulin secretion suggesting that perturbations in the Wnt signaling pathway may contribute substantially to the susceptibility for, and pathogenesis of, type 2 diabetes. This review focuses on considerations of the hormonal regulation of Wnt signaling in islets and implications for mutations in components of the Wnt signaling pathway as a source for risk alleles for type 2 diabetes.

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Acknowledgments

We thank Michael Rukstalis and Melissa Thomas for their helpful comments on this chapter and Sriya Avadhani, Violeta Stanojevic, and Karen McManus for their expert experimental assistance. Effort was supported in part by grants from the US Public Health Service, the American Diabetes Association, and the Juvenile Diabetes Research Foundation.

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  1. Laboratory of Molecular Endocrinology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, 02114, USA

    Joel F. Habener

  2. US Biopharmaceutical Regulatory Affairs Group, Sandoz Inc., A Novartis Company, 506 Carnegie Center, Suite 400, Princeton, NY, 08540, USA

    Zhengyu Liu

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Correspondence to Joel F. Habener .

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  1. Department of Clinical Sciences and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden

    Md. Shahidul Islam

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Habener, J.F., Liu, Z. (2015). Wnt Signaling in Pancreatic Islets. In: Islam, M. (eds) Islets of Langerhans. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6686-0_13

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