Investigating the Role of 17-Beta Estradiol in the Regulation of the Unfolded Protein Response (UPR) in Pancreatic Beta Cells

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2024 Feb 10

PMID 38339098

Authors

Monica De Paoli

Deep Shah

Alexander Zakharia

Zil Patel

Zinal Patel

Pakhi Pakhi

Geoff H Werstuck

Affiliations

Soon will be listed here.

Abstract

Diabetes mellitus is clinically defined by chronic hyperglycemia. Sex differences in the presentation and outcome of diabetes exist with premenopausal women having a reduced risk of developing diabetes, relative to men, or women after menopause. Accumulating evidence shows a protective role of estrogens, specifically 17-beta estradiol, in the maintenance of pancreatic beta cell health; however, the mechanisms underlying this protection are still unknown. To elucidate these potential mechanisms, we used a pancreatic beta cell line (BTC6) and a mouse model of hyperglycemia-induced atherosclerosis, the ApoE:Ins2 mouse, exhibiting sexual dimorphism in glucose regulation. In this study we hypothesize that 17-beta estradiol protects pancreatic beta cells by modulating the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. We observed that ovariectomized female and male ApoE:Ins2 mice show significantly increased expression of apoptotic UPR markers. Sham operated female and ovariectomized female ApoE:Ins2 mice supplemented with exogenous 17-beta estradiol increased the expression of adaptive UPR markers compared to non-supplemented ovariectomized female ApoE:Ins2 mice. These findings were consistent to what was observed in cultured BTC6 cells, suggesting that 17-beta estradiol may protect pancreatic beta cells by repressing the apoptotic UPR and enhancing the adaptive UPR activation in response to pancreatic ER stress.

Citing Articles

The Role of Estrogen across Multiple Disease Mechanisms.

Xiang X, Palasuberniam P, Pare R Curr Issues Mol Biol. 2024; 46(8):8170-8196.

PMID: 39194700 PMC: 11352819. DOI: 10.3390/cimb46080483.

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