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Pancreatic B-cell proliferation and differentiation in animal models of insulin resistance: involvement of the Wnt/beta-catenina signaling pathway


Defective insulin secretion in type 2 diabetes mellitus is caused by beta-cell dysfunction and reduced beta cell mass. A promising way of treatment is using beta cell replacement therapy. So there has been an increasing interest in studying the key pathways implicated in beta-cell proliferation and differentiation. The Wnt/beta-catenin signaling pathway is involved in morphogenesis, cell fate, proliferation and differentiation but its role in the endocrine pancreas plasticity has not been investigated. Hyperplasia/hypertrophy of the beta-cell can occur at certain in vivo and experimental conditions such as in the insulin resistance state. Mice C57BL/6, wild-type and knockout for the LDL receptor (LDLr-/-), fed a high fat diet for a prolonged period, have been used a model of arteriosclerosis, obesity and insulin resistance. The compensatory response of the endxrine pancreas to the diet-induced metabolic alterations has not been thoroughly addressed in these animals. The general aims of this project are: 1) to investigate the functional and morphometric aspects of the endocrine pancreas, focusing on the beta-cells, of both mice, LDLr+/+ e LDLr-/-, that display differences in insulin sensitivity, following exposure to a high-fat diet for short period of time (30 or 60 days) and 2) to study the involvement of the Wnt/beta-catenin signaling pathway in the insulin resistance-induced B-cell hyperplasia in these models. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
OLIVEIRA, R. B.; MASCHIO, D. A.; CARVALHO, C. P. F.; COLLARES-BUZATO, C. B. Influence of gender and time diet exposure on endocrine pancreas remodeling in response to high fat diet-induced metabolic disturbances in mice. ANNALS OF ANATOMY-ANATOMISCHER ANZEIGER, v. 200, p. 88-97, 2015. Web of Science Citations: 18.
D OLIVEIRA, RICARDO B.; CARVALHO, CAROLINA P. D. F.; POLO, CARLA C.; DORIGHELLO, GABRIEL D. G.; BOSCHERO, ANTONIO C.; D OLIVEIRA, HELENA C. F.; COLLARES-BUZATO, CARLA B. Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice. International Journal of Experimental Pathology, v. 95, n. 4, p. 296-308, AUG 2014. Web of Science Citations: 10.
CARVALHO, C. P. F.; OLIVEIRA, R. B.; BRITAN, A.; SANTOS-SILVA, J. C.; BOSCHERO, A. C.; MEDA, P.; COLLARES-BUZATO, C. B. Impaired beta-cell-beta-cell coupling mediated by Cx36 gap junctions in prediabetic mice. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, v. 303, n. 1, p. E144-E151, JUL 2012. Web of Science Citations: 36.

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