Nuclear hormone receptor expression in the endocrine pancreas

Jen Chieh Chuang, Ji Young Cha, James C. Garmey, Raghavendra G. Mirmira, Joyce J. Repa

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

The endocrine pancreas comprises the islets of Langerhans, tiny clusters of cells that contribute only about 2% to the total pancreas mass. However, this little endocrine organ plays a critical role in maintaining glucose homeostasis by the regulated secretion of insulin (by β-cells) and glucagon (by α-cells). The rapid increase in the incidence of diabetes worldwide has spurred renewed interest in islet cell biology. Some of the most widely prescribed oral drugs for treating type 2 diabetes include agents that bind and activate the nuclear hormone receptor, peroxisome proliferator-activated receptor-γ. As a first step in addressing potential roles of peroxisome proliferator-activated receptor-γ and other nuclear hormone receptors (NHRs) in the biology of the endocrine pancreas, we have used quantitative real-time PCR to profile the expression of all 49 members of the mouse NHR superfamily in primary islets, and cell lines that represent α-cells (αTC1) and β-cells (βTC6 and MIN6). In summary, 19 NHR members were highly expressed in both α- and β-cell lines, 13 receptors showed predominant expression (at least an 8-fold difference) in α- vs. β-cell lines, and 10 NHRs were not expressed in the endocrine pancreas. In addition we evaluated the relative expression of these transcription factors during hyperglycemia and found that 16 NHRs showed significantly altered mRNA levels in mouse islets. A similar survey was conducted in primary human islets to reveal several significant differences in NHR expression between mouse and man. These data identify potential therapeutic targets in the endocrine pancreas for the treatment of diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)2353-2363
Number of pages11
JournalMolecular Endocrinology
Volume22
Issue number10
DOIs
StatePublished - Oct 2008

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Cytoplasmic and Nuclear Receptors
Islets of Langerhans
Peroxisome Proliferator-Activated Receptors
Cell Line
Cytotoxic T-Lymphocytes
Glucagon
Hyperglycemia
Type 2 Diabetes Mellitus
Cell Biology
Real-Time Polymerase Chain Reaction
Pancreas
Diabetes Mellitus
Homeostasis
Transcription Factors
Insulin
Glucose
Messenger RNA
Incidence
Therapeutics
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology

Cite this

Nuclear hormone receptor expression in the endocrine pancreas. / Chuang, Jen Chieh; Cha, Ji Young; Garmey, James C.; Mirmira, Raghavendra G.; Repa, Joyce J.

In: Molecular Endocrinology, Vol. 22, No. 10, 10.2008, p. 2353-2363.

Research output: Contribution to journalArticle

Chuang, JC, Cha, JY, Garmey, JC, Mirmira, RG & Repa, JJ 2008, 'Nuclear hormone receptor expression in the endocrine pancreas', Molecular Endocrinology, vol. 22, no. 10, pp. 2353-2363. https://doi.org/10.1210/me.2007-0568
Chuang, Jen Chieh ; Cha, Ji Young ; Garmey, James C. ; Mirmira, Raghavendra G. ; Repa, Joyce J. / Nuclear hormone receptor expression in the endocrine pancreas. In: Molecular Endocrinology. 2008 ; Vol. 22, No. 10. pp. 2353-2363.
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