Hedgehog Signaling Regulation of Insulin Production By Pancreatic -Cells

Hedgehogs (Hhs) are intercellular signaling molecules that regulate tissue patterning in mammalian develop-ment. Mammalian Hhs include Sonic hedgehog (Shh), Indian hedgehog (Ihh), and Desert hedgehog (Dhh). The absence of Shh expression is required for the early development of the endocrine and exocrine pancreas, but whether Hh signaling functions in the fully devel-oped adult endocrine pancreas is unknown. Here we report that Hhs Ihh and Dhh and their receptors patched (Ptc) and smoothened are expressed in the endocrine islets of Langerhans of the fully developed rat pancreas and in the clonal -cell line INS-1. We demon-strate the coexpression of Ptc with insulin in -cells of mouse pancreatic islets, indicating that -cells are tar-gets of active Hh signaling. The administration o