Article

Download article 		Title: Impaired compensatory beta-cell function and growth in response to high-fat diet in LDL receptor knockout mice
Author: Oliveira, Ricardo B. D.; Carvalho, Carolina P. D. F.; Polo, Carla C.; Dorighello, Gabriel D. G.; Boschero, Antônio C.; Oliveira, Helena C. F. D.; Collares-buzato, Carla B.
Year: 2014
Is part of: INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, v. May, p. n/a - n/a
DOI: https://doi.org/10.1111/iep.12084

Citation: Oliveira, Ricardo B. D.; Carvalho, Carolina P. D. F.; Polo, Carla C.; Dorighello, Gabriel D. G.; Boschero, Antônio C.; Oliveira, Helena C. F. D.; 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.May, p. n/a-n/a, 2014

Abstract: In this study, we investigated the effect of low density lipoprotein receptor (LDLr) deficiency on gap junctional connexin 36 (Cx36) islet content and on the functional and growth response of pancreatic beta-cells in C57BL/6 mice fed a high-fat (HF) diet. After 60 days on regular or HF diet, the metabolic state and morphometric islet parameters of wild-type (WT) and LDLr-/- mice were assessed. HF diet-fed WT animals became obese and hypercholesterolaemic as well as hyperglycaemic, hyperinsulinaemic, glucose intolerant and insulin resistant, characterizing them as prediabetic. Also they showed a significant decrease in beta-cell secretory response to glucose. Overall, LDLr-/- mice displayed greater susceptibility to HF diet as judged by their marked cholesterolaemia, intolerance to glucose and pronounced decrease in glucose-stimulated insulin secretion. HF diet induced similarly in WT and LDLr-/- mice, a significant decrease in Cx36 beta-cell content as revealed by immunoblotting. Prediabetic WT mice displayed marked increase in beta-cell mass mainly due to beta-cell hypertrophy/replication. Nevertheless, HF diet-fed LDLr-/- mice showed no significant changes in beta-cell mass, but lower islet-duct association (neogenesis) and higher beta-cell apoptosis index were seen as compared to controls. The higher metabolic susceptibility to HF diet of LDLr-/- mice may be explained by a deficiency in insulin secretory response to glucose associated with lack of compensatory beta-cell expansion.

Keywords: Beta cell; hypercholesterolemia; LDL receptor;
Subjects: CIENCIAS_BIOLOGICAS; Fisiologia Geral; Metabolismo de Lípides e de Carboidratos;

Funding: The authors thank Marta Beatriz Leonardo for the technical assistance, and Ms. Junia C. R. Santos-Silva and Ms. Daniela A. Maschio for helping in the radioimmunoassay and morphometric analysis respectively. This work was funded by grants from FAPESP (2009/52824-1, 2010/50789-1) and CAPES/PROEX (Brazil). RBO and CPFC were recipients of CAPES fellowships (Brazil). 		Financed by: