[Beta]-Cell dedifferentiation, reduced duct cell plasticity, and impaired [Beta]-cell mass regeneration in middle-aged rats

• Published in: American journal of physiology: endocrinology and metabolism Vol. 311; no. 3; p. E554
• Main Authors: Téllez, Noèlia, Vilaseca, Marina, Martí, Yasmina, Pla, Arturo, Montanya, Eduard
• Format: Journal Article
• Language: English
• Published: Bethesda American Physiological Society 01.09.2016
• Subjects: Apoptosis; Cells; Diabetes; Hormones; Risk assessment; Rodents
• ISSN: 0193-1849; 1522-1555

Limitations in β-cell regeneration potential in middle-aged animals could contribute to the increased risk to develop diabetes associated with aging. We investigated β-cell regeneration of middle-aged Wistar rats in response to two different regenerative stimuli: partial pancreatectomy (Px + V) and gastrin administration (Px + G). Pancreatic remnants were analyzed 3 and 14 days after surgery. β-Cell mass increased in young animals after Px and was further increased after gastrin treatment. In contrast, β-cell mass did not change after Px or after gastrin treatment in middle-aged rats. β-Cell replication and individual β-cell size were similarly increased after Px in young and middle-aged animals, and β-cell apoptosis was not modified. Nuclear immunolocalization of neurog3 or nkx6.1 in regenerative duct cells, markers of duct cell plasticity, was increased in young but not in middle-aged Px rats. The pancreatic progenitor-associated transcription factors neurog3 and sox9 were upregulated in islet β-cells of middle-aged rats and further increased after Px. The percentage of chromogranin A+/hormone islet cells was significantly increased in the pancreases of middle-aged Px rats. In summary, the potential for compensatory β-cell hyperplasia and hypertrophy was retained in middle-aged rats, but β-cell dedifferentiation and impaired duct cell plasticity limited β-cell regeneration.