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World J Diabetes. Jun 15, 2021; 12(6): 767-779
Published online Jun 15, 2021. doi: 10.4239/wjd.v12.i6.767
Diabetes and inflammatory diseases: An overview from the perspective of Ca2+/3'-5'-cyclic adenosine monophosphate signaling
Leandro Bueno Bergantin
Leandro Bueno Bergantin, Department ofPharmacology, Universidade Federal de São Paulo, São Paulo 04039-032, Brazil
Author contributions: Bergantin LB is the sole author; Bergantin L participated in the whole process of the study.
Conflict-of-interest statement: The author declares no conflict of interest, financial or otherwise.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Leandro Bueno Bergantin, PhD, Professor, Department of Pharmacology, Universidade Federal de São Paulo, Rua Pedro de Toledo, 669–Vila Clementino, São Paulo 04039-032, Brazil. leanbio39@yahoo.com.br
Received: December 2, 2020
Peer-review started: December 2, 2020
First decision: December 24, 2020
Revised: December 29, 2020
Accepted: March 7, 2021
Article in press: March 7, 2021
Published online: June 15, 2021
Abstract

A large amount of evidence has supported a clinical link between diabetes and inflammatory diseases, e.g., cancer, dementia, and hypertension. In addition, it is also suggested that dysregulations related to Ca2+ signaling could link these diseases, in addition to 3'-5'-cyclic adenosine monophosphate (cAMP) signaling pathways. Thus, revealing this interplay between diabetes and inflammatory diseases may provide novel insights into the pathogenesis of these diseases. Publications involving signaling pathways related to Ca2+ and cAMP, inflammation, diabetes, dementia, cancer, and hypertension (alone or combined) were collected by searching PubMed and EMBASE. Both signaling pathways, Ca2+ and cAMP signaling, control the release of neurotransmitters and hormones, in addition to neurodegeneration, and tumor growth. Furthermore, there is a clear relationship between Ca2+ signaling, e.g., increased Ca2+ signals, and inflammatory responses. cAMP also regulates pro- and anti-inflammatory responses. Due to the experience of our group in this field, this article discusses the role of Ca2+ and cAMP signaling in the correlation between diabetes and inflammatory diseases, including its pharmacological implications. As a novelty, this article also includes: (1) A timeline of the major events in Ca2+/cAMP signaling; and (2) As coronavirus disease 2019 (COVID-19) is an emerging and rapidly evolving situation, this article also discusses recent reports on the role of Ca2+ channel blockers for preventing Ca2+ signaling disruption due to COVID-19, including the correlation between COVID-19 and diabetes.

Keywords: Diabetes, Cancer, Hypertension, Dementia, Ca2+/3'-5'-cyclic adenosine monophosphate signaling, Ca2+ channel blockers, Pharmacotherapy, Neurodegeneration, COVID-19

Core Tip: There are several reviews in the literature on diabetes and inflammatory diseases. Nonetheless, to my knowledge, this is the first review which clearly discusses the role of Ca2+/3'-5'-cyclic adenosine monophosphate (cAMP) signaling in the link between diabetes and inflammatory diseases. This article also includes a timeline of the major events in Ca2+/cAMP signaling, and discusses recent reports on the role of Ca2+ channel blockers for preventing Ca2+ signaling disruption due to coronavirus disease 2019 (COVID-19), including the correlation between COVID-19 and diabetes.