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Morphogenetic plasticity of adult human pancreatic islets of Langerhans

2005; Springer Nature; Volume: 12; Issue: 7 Linguagem: Inglês

10.1038/sj.cdd.4401617

1476-5403

A-M Jamal, Mark Lipsett, Robert Sladek, Sylvie Laganière, Stephen Hanley, Lynn Rosenberg,

Diabetes Management and Research

The aim of this study was to investigate the phenotypic plasticity of pancreatic islets of Langerhans. Quiescent adult human islets were induced to undergo a phenotypic switch to highly proliferative duct-like structures in a process characterized by a loss of expression of islet-specific hormones and transcription factors as well as a temporally related rise in the expression of markers of both duct epithelial and progenitor cells. Short-term treatment of these primitive duct-like structures with the neogenic factor islet neogenesis-associated protein (INGAP104–118) induced their reconversion back to islet-like structures in a PI3-kinase-dependent manner. These neoislets resembled freshly isolated human islets with respect to the presence and topological arrangement of the four endocrine cell types, islet gene expression and hormone production, insulin content and glucose-responsive insulin secretion. Our results suggest that adult human islets possess a remarkable degree of morphogenetic plasticity. This novel observation may have important implications for understanding pancreatic carcinogenesis and islet neogenesis.