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Research Resource: Nuclear Hormone Receptor Expression in the Endocrine Pancreas

Departments of Physiology (J.-C.C., J.-Y.C., J.J.R.) and Internal Medicine (J.J.R.), University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077; Department of Internal Medicine, Division of Endocrinology and Metabolism (J.C.G), University of Virginia Health System, Charlottesville, Virginia 22903; and Department of Pediatrics and the Wells Center for Pediatric Research (R.G.M.), Indiana University School of Medicine, Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Joyce J. Repa, Ph.D., Departments of Physiology and Internal Medicine, Touchstone Center for Diabetes Research, Division for Hypothalamic Research-Y6.322C, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9077. E-mail: joyce.repa{at}utsouthwestern.edu.

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 -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-. As a first step in addressing potential roles of peroxisome proliferator-activated receptor- 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 -cells (TC1) and β-cells (βTC6 and MIN6). In summary, 19 NHR members were highly expressed in both - and β-cell lines, 13 receptors showed predominant expression (at least an 8-fold difference) in - 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.

NURSA Molecule Pages Link:

Nuclear Receptors:   DAX1  |  SHP  |  TRα  |  TRβ  |  RARα  |  RARβ  |  RARγ  |  PPARα  |  PPARδ  |  PPARγ  |  REV-ERBα  |  REV-ERBβ  |  RORα  |  RORβ  |  RORγ  |  LXRβ  |  LXRα  |  FXRα  |  FXRβ  |  VDR  |  PXR  |  CAR  |  HNF4α  |  HNF4γ  |  HNF4β  |  RXRα  |  RXRβ  |  RXRγ  |  TR2  |  TR4  |  TLX  |  PNR  |  COUP-TFI  |  COUP-TFII  |  EAR-2  |  ERα  |  ERβ  |  ERRα  |  ERRβ  |  ERRγ  |  GR  |  MR  |  PR  |  AR  |  NGFIB  |  NURR1  |  NOR1  |  SF-1  |  LRH-1  |  GCNF