August 1, 2015 admin

Islet-1 is essential for pancreatic β-cell function

Ediger BN, Du A, Liu J, Hunter CS, Walp ER, Schug J, Kaestner KH, Stein R, Stoffers DA, May CL.

Diabetes. 2014 Dec;63(12):4206-17.

Islet-1 (Isl-1) is essential for the survival and ensuing differentiation of pancreatic endocrine progenitors. Isl-1 remains expressed in all adult pancreatic endocrine lineages; however, its specific function in the postnatal pancreas is unclear. Here we determine whether Isl-1 plays a distinct role in the postnatal β-cell by performing physiological and morphometric analyses of a tamoxifen-inducible, β-cell-specific Isl-1 loss-of-function mouse: Isl-1(L/L); Pdx1-CreER(Tm). Ablating Isl-1 in postnatal β-cells reduced glucose tolerance without significantly reducing β-cell mass or increasing β-cell apoptosis. Rather, islets from Isl-1(L/L); Pdx1-CreER(Tm) mice showed impaired insulin secretion. To identify direct targets of Isl-1, we integrated high-throughput gene expression and Isl-1 chromatin occupancy using islets from Isl-1(L/L); Pdx1-CreER(Tm) mice and βTC3 insulinoma cells, respectively. Ablating Isl-1 significantly affected the β-cell transcriptome, including known targets Insulin and MafA as well as novel targets Pdx1 and Slc2a2. Using chromatin immunoprecipitation sequencing and luciferase reporter assays, we found that Isl-1 directly occupies functional regulatory elements of Pdx1 and Slc2a2. Thus Isl-1 is essential for postnatal β-cell function, directly regulates Pdx1 and Slc2a2, and has a mature β-cell cistrome distinct from that of pancreatic endocrine progenitors.

Access full article: http://diabetes.diabetesjournals.org/content/early/2014/07/15/db14-0096.full.pdf

Supported File Formats:


  • – Non Proprietary (JPG, TIF)
  • – 3D Histech (MRXS)
  • – Aperio (SVS, AFI, eSlideManager)
  • – Hamamatsu (NDPI, NDPIS)
  • – Leica (SVS, SCN, LIF)
  • – Mikroscan (TIF)
  • – Nikon (ND2)
  • – Olympus (VSI)
  • – Perkin Elmer (QPTIFF, Vectra TIF)
  • – Philips IMS
  • – Zeiss (CZI)

Don’t see the format you’re looking for? Contact us to make a request

CLOSE
Thank you for signing-up. Please check your email for link to access webinar recording.