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

Grant number: 09/52824-1
Support Opportunities:Regular Research Grants
Duration: November 01, 2009 - April 30, 2012
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Carla Beatriz Collares Buzato
Grantee:Carla Beatriz Collares Buzato
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


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)
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, . (10/50789-1, 09/52824-1)
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, . (10/50789-1, 09/52824-1)
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, . (10/50789-1, 09/52824-1)

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