DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2011; 27: 755–760. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.1247 Delta-cell-specific expression of hedgehog pathway Ptch1 receptor in murine and human endocrine pancreas F. A. Grieco 1,2 M. Moretti 3 G. Sebastiani 1,2 L. Galleri 1,2 I. Spagnuolo 1,2 G. Scafetta 3 A. Gulino 3 E. De Smaele 4 M. Maroder 5 F. Dotta 1,2∗ 1 Diabetes Unit, Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Seina, Italy 2 Umberto Di Mario ONLUS Research Foundation, c/o Toscana Life Sciences Park, Siena, Italy 3 Department of Molecular Medicine, University of Rome ‘‘Sapienza’’, Rome, Italy 4 Department of Experimental Medicine, University of Rome ‘‘Sapienza’’, Rome, Italy 5 Department of Medico-Surgical Sciences and Biotechnologies, University of Rome ‘‘La Sapienza’’, Latina, Italy ∗ Correspondence to: F. Dotta, U.O. Diabetologia, University of Siena, Policlinico ‘‘Le Scotte’’, No. 3 Lotto-5S, Viale Bracci 18, 53100 Siena, Italy E-mail: francesco.dotta@alice.it Received : 2 March 2011 Revised: 30 May 2011 Accepted: 8 June 2011 Abstract Background Hedgehog pathway plays an important role during pancreas development, when its inactivation is crucial to assure expression of pancreatic marker genes involved in the organ formation and to assure an appropriate organogenesis. Patched1 (Ptch1) is a transmembrane receptor of hedgehog pathway which has a key role in this process. In fact, heterozygous Ptch1 mutant (ptc +/− ) mice are affected by an impaired glucose tolerance accompanied by reduced islet function. In the light that the cell distribution of Ptch1 receptor within the endocrine pancreas has not yet been established, we aimed at identifying the pancreatic endocrine cell subset(s) expressing such molecule. Methods Double immunostaining for Ptch1 and pancreatic hormones insulin, glucagon and somatostatin on pancreatic paraffin sections of C57BL/6J mice and human non-diabetic multiorgan donors was performed and analysed using confocal microscopy. In addition, diabetes was experimentally induced in mice by intraperitoneal injection of streptozotocin. Quantitative real-time polymerase chain reaction after laser-capture microdissection of different islets from frozen pancreatic murine tissue sections was also performed. Results Ptch1 receptor was detected only in somatostatin-positive delta cells both in mice and in human pancreas; in mice its expression was not affected by streptozotocin treatment. A significant increase of Ptch1 mRNA expression levels in the islet periphery versus the islet core was observed by quantitative real-time polymerase chain reaction, in accord with immunohistochemical observations. Conclusion Our data show a delta-cell-specific expression of Ptch1 receptor in murine and human pancreas. Copyright  2011 John Wiley & Sons, Ltd. Keywords hedgehog pathway; Ptch1; somatostatin; endocrine pancreas; diabetes Introduction A decreased functional beta-cell mass is the hallmark of both type 1 and type 2 diabetes mellitus, but the molecular mechanisms involved in the regulation of beta-cell mass during the disease are still not fully understood. A detailed comprehension of these molecular processes may provide basic principles for new therapeutic approaches for treating diabetes. It has been observed that hedgehog signalling pathway regulates organ formation and tissue patterning of several organs during development in Copyright  2011 John Wiley & Sons, Ltd.