Multiple endocrine neoplasia type 1 deletion in pancreatic α-cells leads to development of insulinomas in mice

H. C Jennifer Shen, Kris Ylaya, Klaus Pechhold, Arianne Wilson, Asha Adem, Stephen M. Hewitt, Steven K. Libutti

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The pancreatic α- and β-cells are critical components in regulating blood glucose homeostasis via secretion of glucagon and insulin, respectively. Both cell types are typically localized in the islets of Langerhans. However, little is known about the roles of paracrine interactions that contribute to their physiological functions. The lack of suitable cell lines to study α- and β-cells interactions have led us to develop an α-cell-specific Cre-expressing transgenic line utilizing a glucagon promoter sequence, the Glu-Cre transgenic mouse. Here, we demonstrate that the Glu-Cre could specifically and efficiently excise floxed target genes in adult islet α-cells. We further showed that deletion of the tumor suppressor gene, multiple endocrine neoplasia type 1 (Men1), in α-cells led to tumorigenesis. However, to our surprise, the lack of Men1 in α-cells did not result in glucagonomas but rather β-cell insulinomas. Because deletion of the Men1 alleles was only present in α-cells, our data suggested that cross communication between α- and β-cells contributes to tumorigenesis in the absence of Men1. Together, we believed that the new model systems described here will allow future studies to decipher cellular interactions between islet α- and β-cells in a physiological context.

Original languageEnglish (US)
Pages (from-to)4024-4030
Number of pages7
JournalEndocrinology
Volume151
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Multiple Endocrine Neoplasia Type 1
Insulinoma
Islets of Langerhans
Glucagon
Cell Communication
Carcinogenesis
Glucagonoma
Cellular Structures
Tumor Suppressor Genes
Transgenic Mice
Blood Glucose
Homeostasis
Alleles
Insulin
Cell Line
Genes

ASJC Scopus subject areas

  • Endocrinology

Cite this

Shen, H. C. J., Ylaya, K., Pechhold, K., Wilson, A., Adem, A., Hewitt, S. M., & Libutti, S. K. (2010). Multiple endocrine neoplasia type 1 deletion in pancreatic α-cells leads to development of insulinomas in mice. Endocrinology, 151(8), 4024-4030. https://doi.org/10.1210/en.2009-1251

Multiple endocrine neoplasia type 1 deletion in pancreatic α-cells leads to development of insulinomas in mice. / Shen, H. C Jennifer; Ylaya, Kris; Pechhold, Klaus; Wilson, Arianne; Adem, Asha; Hewitt, Stephen M.; Libutti, Steven K.

In: Endocrinology, Vol. 151, No. 8, 08.2010, p. 4024-4030.

Research output: Contribution to journalArticle

Shen, HCJ, Ylaya, K, Pechhold, K, Wilson, A, Adem, A, Hewitt, SM & Libutti, SK 2010, 'Multiple endocrine neoplasia type 1 deletion in pancreatic α-cells leads to development of insulinomas in mice', Endocrinology, vol. 151, no. 8, pp. 4024-4030. https://doi.org/10.1210/en.2009-1251
Shen, H. C Jennifer ; Ylaya, Kris ; Pechhold, Klaus ; Wilson, Arianne ; Adem, Asha ; Hewitt, Stephen M. ; Libutti, Steven K. / Multiple endocrine neoplasia type 1 deletion in pancreatic α-cells leads to development of insulinomas in mice. In: Endocrinology. 2010 ; Vol. 151, No. 8. pp. 4024-4030.
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