Characterization of B cell plasticity in an original in vivo mouse model
(2012)
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- (en) The common observation of pathological specimens of human endocrine pancreas has repeatedly raised questions. Among those, one is recurrent: what is the mechanism underlying the adaptation of the human endocrine pancreas to face the increased or lowered needs of insulin, does it solely rely on changes in β cell function or does it also depend on changes in the β cell mass ; in other words, the question is whether and how the endocrine pancreas is able to undergo hyperplasia and atrophy in relation to the changes in insulin needs and whether the endocrine pancreas could be considered as a “plastic” organ? Among the rationales that generate these questions are the analyses of the pancreases of infants suffering from persistent hypoglycemic hyperinsulinemia bearing a focal lesion hypersecreting insulin. Surprisingly, this localized abnormal insulin hypersecretion seems to induce the resting and atrophy of the islets of Langerhans located in the healthy part of the pancreas. No experimental model was adapted to the study of this pathology and of the mechanisms underlying atrophy of the normal islets surrounding the abnormal source of insulin hypersecretion and recovery after its resection. The purpose of this thesis has been to develop and characterize a model inducing plasticity of β cells. This model had to be flexible, specific to β cells and convenient for the study of β cell plasticity, defined as the dynamic adjustment of β cell mass and function to ensure normoglycemia through changing metabolic circumstances (Kargar and Ktorza 2008). We developed a model based on the implantation of insulin pellets inducing hyperinsulinaemia and concomitant profound atrophy of β cells. After the removal of these insulin implants, an impressive and rapid reconstitution of β cell mass occurred, mainly achieved through the replication of pre-existing β cells. We then decided to investigate whether regenerative mechanisms, in addition to the replication of pre-existing β cells, would require the reactivation of transcription factors that recapitulate the molecular events of embryogenesis and lead to the sequential differentiation of islet cells. Consequently, we explored the expression of several of these transcription factors using real-time PCR (RTqPCR) after laser capture microdissection (LCM) allowing a selective isolation of islets from surrounding cells in tissue sections. These findings were correlated with cellular localisation of the proteins revealed by immunofluorescence technique
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Nollevaux, M.-C. (2012). Characterization of B cell plasticity in an original in vivo mouse model. https://hdl.handle.net/2078.5/75651