Morphogenetic plasticity of adult human pancreatic islets of Langerhans.
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.
Jamal
A-M
AM
Department of Surgery, McGill University, Montréal, Canada.
Lipsett
M
M
Sladek
R
R
Laganière
S
S
Hanley
S
S
Rosenberg
L
L
D000328:Adult; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000951:Antigens, Neoplasm / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology* / Q000187:drug effects; D007633:Keratins / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism*; D009024:Morphogenesis; D010183:Pancreatic Ducts / Q000166:cytology / Q000187:drug effects; D000073718:Pancreatitis-Associated Proteins; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology; D000077191:Wortmannin
D000730:Androstadienes; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D005419:Flavonoids; D037181:Lectins, C-Type; D000073718:Pancreatitis-Associated Proteins; D047428:Protein Kinase Inhibitors; C000612141:REG3A protein, human; D007633:Keratins; D019869:Phosphatidylinositol 3-Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin