Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types-Reference-Cited by-同舟云学术

Zinc-chelating BET bromodomain inhibitors equally target islet endocrine cell types

Published:2024-06-01 Issue:6 Volume:326 Page:R515-R527
ISSN:0363-6119
Container-title:American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
language:en
Short-container-title:American Journal of Physiology-Regulatory, Integrative and Comparative Physiology

Author:

Jones Lipinski Rachel A.¹²^ORCID,Stancill Jennifer S.¹,Nuñez Raymundo¹,Wynia-Smith Sarah L.¹,Sprague Daniel J.²³⁴^ORCID,Nord Joshua A.¹⁴,Bird Amir¹,Corbett John A.¹^ORCID,Smith Brian C.¹²⁴^ORCID

Affiliation:

1. Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

2. Program in Chemical Biology, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

3. Department of Cell Biology, Neurobiology, and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

4. Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin, United States

Abstract

Inhibition of BET bromodomains is a novel potential strategy to prevent and treat diabetes mellitus. However, BET inhibitors have negative side effects. We synthesized a BET inhibitor expected to exploit the high zinc concentration in β cells to accumulate in β cells. We show our inhibitor targeted pancreatic endocrine cells; however, it was less effective in immune cells. A control inhibitor showed the opposite effect. These findings help us understand how to target specific cells in diabetes treatment.

Funder

Juvenile Diabetes Research Foundation

American Diabetes Association

American Heart Association

HHS | NIH | National Heart, Lung, and Blood Institute

HHS | NIH | National Institute of Allergy and Infectious Diseases

HHS | NIH | National Institute of Diabetes and Digestive and Kidney Diseases

Publisher

American Physiological Society

Link

https://journals.physiology.org/doi/pdf/10.1152/ajpregu.00259.2023

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