德国马克斯·普朗克生物物理化学研究所研究人员通过激活患糖尿病老鼠胰腺细胞的一种基因，使一些胰腺细胞转化为能分泌胰岛素的细胞。这一成果为糖尿病治疗研究带来了新思路。
胰岛β细胞具有分泌胰岛素并以此降血糖的功能，而胰高血糖素的作用与胰岛素相反，能使血糖升高，两者共同作用可以调节机体血糖平衡。德国研究人员发现，通过激活患糖尿病老鼠的胰腺细胞Pax4基因，不仅可以使胰腺分泌的前体细胞转化为能分泌胰岛素的胰岛β细胞，而且还能使原来分泌胰高血糖素的细胞转化为胰岛β细胞。
参与这项研究的专家说，在老鼠身上发现的上述基因调节机制能否用于人还需更多研究加以证实。如果将来可以依据上述发现研发糖尿病药物，还需要考虑各种因素，例如不能导致胰岛β细胞过多生成，否则会破坏胰岛素和胰高血糖素之间的微妙平衡。
这一研究成果已发表在新一期美国学术期刊《细胞》（Cell）上。（生物谷Bioon.com）
生物谷推荐原始出处：
Cell, Volume 138, Issue 3, 449-462, 7 August 2009 doi:10.1016/j.cell.2009.05.035
The Ectopic Expression of Pax4 in the Mouse Pancreas Converts Progenitor Cells into and Subsequently Cells
Patrick Collombat1,2,3,11,,,Xiaobo Xu4,Philippe Ravassard3,5,Beatriz Sosa-Pineda6,Sébastien Dussaud5,7,Nils Billestrup8,Ole D. Madsen2,3,9,Palle Serup2,3,9,Harry Heimberg2,3,4andAhmed Mansouri1,2,10,,
1 Department of Molecular Cell Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, D-37077 G?ttingen, Germany
2 Beta Cell Biology Consortium, 2213 Garland Avenue, 9465 MRB IV, Nashville, TN 37323-0494, USA
3 JDRF Center for Beta Cell Therapy in Diabetes, Laarbeeklaan 103, B-1090 Brussels, Belgium
4 Diabetes Research Center, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium
5 Biotechnology and Biotherapy Laboratory, Centre de Recherche de l'Institut du Cerveau et de la Moelle, CNRS UMR 7225, INSERM UMRS 975, University Pierre et Marie Curie, H?pital Pitié Salpêtrière, FR-75013 Paris, France
6 Department of Genetics/Tumor Cell Biology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA
7 Centre d'Expérimentation Fonctionnelle, Pitié Salpêtrière Medical Faculty, Université Pierre et Marie Curie, FR-75013 Paris, France
8 Department of Translational Diabetology Research Institute, Hagedorn Niels Steensensvej 6, DK-2820 Gentofte, Denmark
9 Department of Developmental Biology Research Institute, Hagedorn Niels Steensensvej 6, DK-2820 Gentofte, Denmark
10 Department of Clinical Neurophysiology, University of Göttingen, Robert-Koch Strasse 40, D-37075 G?ttingen, Germany
We have previously reported that the loss of Arx and/or Pax4 gene activity leads to a shift in the fate of the different endocrine cell subtypes in the mouse pancreas, without affecting the total endocrine cell numbers. Here, we conditionally and ectopically express Pax4 using different cell-specific promoters and demonstrate that Pax4 forces endocrine precursor cells, as well as mature α cells, to adopt a β cell destiny. This results in a glucagon deficiency that provokes a compensatory and continuous glucagon+ cell neogenesis requiring the re-expression of the proendocrine gene Ngn3. However, the newly formed β cells fail to correct the hypoglucagonemia since they subsequently acquire a β cell phenotype upon Pax4 ectopic expression. Notably, this cycle of neogenesis and redifferentiation caused by ectopic expression of Pax4 in β cells is capable of restoring a functional β cell mass and curing diabetes in animals that have been chemically depleted of β cells.
