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?-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

ABSTRACT: The existence of adult ?-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that ?-cell progenitors can be activated by ductal ligation-induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional ?-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to ?-cell mass expansion. Rather, PDL stimulates massive pancreatic injury, which alters pancreatic composition and thus complicates accurate measurement of ?-cell content via traditional morphometry methodologies that superficially sample the pancreas. To overcome this potential bias, we quantified ?-cells from the entire pancreas and observed that ?-cell mass and insulin content are totally unchanged by PDL-induced injury. Lineage-tracing studies using sequential administration of thymidine analogs, rat insulin 2 promoter-driven cre-lox, and low-frequency ubiquitous cre-lox reveal that PDL does not convert progenitors to the ?-cell lineage. Thus, we conclude that ?-cells are not generated in injured adult mouse pancreas.

SUBMITTER: Rankin MM

PROVIDER: S-EPMC3636617 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

Rankin Matthew M MM Wilbur Christopher J CJ Rak Kimberly K Shields Emily J EJ Granger Anne A Kushner Jake A JA

Diabetes 20130124 5

The existence of adult β-cell progenitors remains the most controversial developmental biology topic in diabetes research. It has been reported that β-cell progenitors can be activated by ductal ligation-induced injury of adult mouse pancreas and apparently act in a cell-autonomous manner to double the functional β-cell mass within a week by differentiation and proliferation. Here, we demonstrate that pancreatic duct ligation (PDL) does not activate progenitors to contribute to β-cell mass expan ...[more]

PMID: 23349489

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Project description:Liver dysfunction and cirrhosis affect vasculature in several organ systems and cause impairment of organ functions, thereby increasing morbidity and mortality. If a mouse model of hepatopulmonary syndrome (HPS) could be established, greater insight into the genetic basis of the disease would be gained. Our objectives were to establish a mouse model of lung injury after common bile duct ligation (CBDL) and to investigate pulmonary pathogenesis for application in future therapeutic approaches. Balb/c mice were subjected to CBDL. Immunohistochemical analyses and real-time quantitative reverse transcriptional polymerase chain reaction were performed on pulmonary tissues. The presence of HPS markers were detected by western blot and microarray analyses. We observed extensive proliferation of CD31-positive pulmonary vascular endothelial cells 2 weeks after CBDL, and identified 11 up-regulated and 8 down-regulated proteins that were associated with angiogenesis. MMP-9 protein was highly expressed at 3 weeks after CBDL, and less expressed in lungs of the control group. Contrary to our expectation, lung pathology in our mouse model exhibited differences from that of rat models, and the mechanisms responsible for these differences are unknown. This phenomenon may be explained by contrasting processes related to TNF induction of angiogenic signaling pathways in the inflammatory phase; thus, we suggest that our mouse model can be applied to pulmonary pathological analyses in the inflammatory phase, i.e., to systemic inflammatory response syndrome, acute lung injury, and MOD syndrome. After induction of anesthesia, a median abdominal incision was made and the common bile duct was identified. The duct was dissected carefully under a microscope, and doubly ligated with 7-0 Prolene and transected. In the sham operation (control) group, the duct was dissected without common bile duct ligation. Mice were sacrificed at 2 and 3 weeks after surgery. CD31-positive cells were assembled from three mice in each group.

Dataset Information

?-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

Publications

β-Cells are not generated in pancreatic duct ligation-induced injury in adult mice.

Similar Datasets

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