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|Title:||The Role Of 17-beta-estradiol And Estrogen Receptors On Glucose Homeostasis In Malnourishment Mice|
The role of 17-beta-estradiol and estrogen receptors on glucose homeostasis in malnourishment mice
Leite, N. C.
Vettorazzi, J. F.
Costa-Júnior, J. M.
Borck, P. C.
Boschero, A. C.
Carneiro, E. M.
|Abstract:||Malnourishment mice show low insulin plasma level and a reduced insulin secretion. To maintain the normal glucose homeostasis, these animals increased insulin sensitivity on peripheral tissues. Estrogen receptors (ERs) are implicated in insulin secretion and biosynthesis, as well as, insulin sensitivity. The aim of this study was to verify the role of ER and estradiol upon glycemic control of male malnourished mice. Post-weaned Swiss male mice were fed with normoprotein diet (14%, NP) or low protein diet (6%, LP) protein diet during 8 weeks. We characterized the malnourishment phenotype through analyses of the body weight, insulin, protein and albumin plasma levels. We analyzed the gene expression and protein content of estrogen receptor (ER) in the liver, adipose tissue, skeletal muscle and pancreatic islets. We measured the effect of 10μg/Kg of E2 on the insulin sensitivity with a hyperinsulinemic-euglycemic clamp assay, and also, the effect of 1nM estradiol (E2) on in-vitro glucose stimulated insulin secretion (GSIS). Data are expressed as mean ± SEM and statistical significance was determined using two-tailed T-test. Low protein diet (6%) induced the malnourishment phenotype, indicated by a lower body weight (control: 40.43±3.9g; LP: 35.83±1.99g; p-value:0.0001), lower plasma levels of protein (control: 5.61±0.23g/dL; LP: 4.86±0. 19g/dL; p-value:0.02), albumin (control: 2.16±0.07g/dL; LP: 1.92±0.07g/dL; p-value:0.02) and insulin (control: 2.94±0.51ng/mL; LP:1.20±0.18ng/mL; p-value:0.002) compared with the control group. The analysis of estrogen receptor gene expression showed, in liver, a down regulation of ERα and an up regulation of ERβ in LP animals; a decreased expression in both isoforms in adipose tissue; and a higher expression of both receptors in muscle. In pancreatic islets, ERα was increased in LP mice but ERβ did not change. The protein content of estrogen receptors did not show changes in any tissues in LP animals compared with control. The stimulation with 10μg/Kg of E2 in a hyperinsulinemic-euglycemic clamp showed a statistically significant increase in glucose infusion rate in LP group compared with control (basal phase: control 0.57±0.08mL/min; LP 0.89±0.1mL/min; pvalue:0.005).This date indicates increased insulin sensitivity in LP mice. GSIS was increased when islets from LP animals were stimulated with 10nM E2 in low and intermedia glucose concentration compared with control group (2.8mM glucose: control: 0.54ng/mL·ng protein-1; LP: 1.17ng/mL·ng protein-1; 8.3mM glucose: control:1.45ng/mL·ng protein1 ; LP: 2.88ng/mL·ng protein-1; 16.6mM glucose: control: 3.36ng/mL·ng protein-1; LP: 4.01ng/mL·ng protein-1); these changes were statistically significant (p-value:0.04). : We conclude that the effects of steroid hormone augmented insulin secretion and action in malnourishment mice may be through mechanisms independent of ER protein express.|
Insulina - Secreção
|Citation:||Diabetologia. Springer, v. 59, p. S327 - S327, 2016.|
|Appears in Collections:||IB - Artigos e Outros Documentos|
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