Diabetes, Inflammation, and the Adiponectin Paradox: Therapeutic Targets in SARS-CoV-2

Overview

Journal Drug Discov Today

Specialty Pharmacology

Date 2021 Mar 29

PMID 33775925

Citations 10

Authors

Gilbert Ho

Alysha Ali

Yoshiki Takamatsu

Ryoko Wada

Eliezer Masliah

Makoto Hashimoto

Affiliations

Soon will be listed here.

Abstract

Aging and pre-existing conditions in older patients increase severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) severity and its complications, although the causes remain unclear. Apart from acute pulmonary syndrome, Coronavirus 2019 (COVID-19) can increasingly induce chronic conditions. Importantly, SARS-CoV-2 triggers de novo type 2 diabetes mellitus (T2DM) linked to age-associated cardiovascular disease (CVD), cancers, and neurodegeneration. Mechanistically, SARS-CoV-2 induces inflammation, possibly through damage-associated molecular pattern (DAMP) signaling and 'cytokine storm,' causing insulin resistance and the adiponectin (APN) paradox, a phenomenon linking metabolic dysfunction to chronic disease. Accordingly, preventing the APN paradox by suppressing APN-related inflammatory signaling might prove beneficial. A better understanding could uncover novel therapies for SARS-CoV-2 and its chronic disorders.

Citing Articles

The Relationship between the Laboratory Biomarkers of SARS-CoV-2 Patients with Type 2 Diabetes at Discharge and the Severity of the Viral Pathology.

Restea P, Tigan S, Vicas L, Fritea L, Muresan M, Manole F J Pers Med. 2024; 14(6).

PMID: 38929867 PMC: 11204915. DOI: 10.3390/jpm14060646.

Are adipokines related to COVID-19 and its severity? A systematic review and meta-analysis.

Ismaiel A, Birkhahn L, Leucuta D, Al Srouji N, Popa S, Dumitrascu D Med Pharm Rep. 2024; 97(2):120-131.

PMID: 38746027 PMC: 11090279. DOI: 10.15386/mpr-2624.

Consequences of COVID-19 on Adipose Tissue Signatures.

Krupka S, Hoffmann A, Jasaszwili M, Dietrich A, Guiu-Jurado E, Kloting N Int J Mol Sci. 2024; 25(5).

PMID: 38474155 PMC: 10932458. DOI: 10.3390/ijms25052908.

Organokines in COVID-19: A Systematic Review.

Barbalho S, Minniti G, Miola V, Dos Santos Haber J, Cincotto Dos Santos Bueno P, Santos de Argollo Haber L Cells. 2023; 12(10).

PMID: 37408184 PMC: 10216619. DOI: 10.3390/cells12101349.

The potential molecular implications of adiponectin in the evolution of SARS-CoV-2: Inbuilt tendency.

Al-Kuraishy H, Al-Gareeb A, Bungau S, Radu A, El-Saber Batiha G J King Saud Univ Sci. 2022; 34(8):102347.

PMID: 36211634 PMC: 9524222. DOI: 10.1016/j.jksus.2022.102347.

References

Liu M, Liu F . Up- and down-regulation of adiponectin expression and multimerization: mechanisms and therapeutic implication. Biochimie. 2012; 94(10):2126-30. PMC: 3542391. DOI: 10.1016/j.biochi.2012.01.008. View

Jiang Y, Yi C, Yi Y, Jin Q, Kang A, Li J . Adiponectin exacerbates influenza infection in elderly individuals via IL-18. Signal Transduct Target Ther. 2020; 5(1):32. PMC: 7118100. DOI: 10.1038/s41392-020-0141-y. View

Lee C, Lui D, Cheung C, Fong C, Yuen M, Chow W . Higher Circulating Adiponectin Concentrations Predict Incident Cancer in Type 2 Diabetes - The Adiponectin Paradox. J Clin Endocrinol Metab. 2020; 105(4). DOI: 10.1210/clinem/dgaa075. View

Bindom S, Hans C, Xia H, Boulares A, Lazartigues E . Angiotensin I-converting enzyme type 2 (ACE2) gene therapy improves glycemic control in diabetic mice. Diabetes. 2010; 59(10):2540-8. PMC: 3279528. DOI: 10.2337/db09-0782. View

Duncan B, Schmidt M, Pankow J, Bang H, Couper D, Ballantyne C . Adiponectin and the development of type 2 diabetes: the atherosclerosis risk in communities study. Diabetes. 2004; 53(9):2473-8. DOI: 10.2337/diabetes.53.9.2473. View

Hashimoto M, Ho G, Takamatsu Y, Shimizu Y, Sugama S, Takenouchi T . Evolvability and Neurodegenerative Disease: Antagonistic Pleiotropy Phenomena Derived from Amyloid Aggregates. J Parkinsons Dis. 2018; 8(3):405-408. PMC: 6130413. DOI: 10.3233/JPD-181365. View

Shah V, Firmal P, Alam A, Ganguly D, Chattopadhyay S . Overview of Immune Response During SARS-CoV-2 Infection: Lessons From the Past. Front Immunol. 2020; 11:1949. PMC: 7426442. DOI: 10.3389/fimmu.2020.01949. View

Su D, Coudriet G, Kim D, Lu Y, Perdomo G, Qu S . FoxO1 links insulin resistance to proinflammatory cytokine IL-1beta production in macrophages. Diabetes. 2009; 58(11):2624-33. PMC: 2768186. DOI: 10.2337/db09-0232. View

Skrip L, Derra K, Kabore M, Noori N, Gansane A, Valea I . Clinical management and mortality among COVID-19 cases in sub-Saharan Africa: A retrospective study from Burkina Faso and simulated case analysis. Int J Infect Dis. 2020; 101:194-200. PMC: 7518969. DOI: 10.1016/j.ijid.2020.09.1432. View

10.

Jain A, Chaurasia R, Sengar N, Singh M, Mahor S, Narain S . Analysis of vitamin D level among asymptomatic and critically ill COVID-19 patients and its correlation with inflammatory markers. Sci Rep. 2020; 10(1):20191. PMC: 7677378. DOI: 10.1038/s41598-020-77093-z. View

11.

Hulsmans M, Van Dooren E, Mathieu C, Holvoet P . Decrease of miR-146b-5p in monocytes during obesity is associated with loss of the anti-inflammatory but not insulin signaling action of adiponectin. PLoS One. 2012; 7(2):e32794. PMC: 3290617. DOI: 10.1371/journal.pone.0032794. View

12.

Chen L, Long X, Xu Q, Tan J, Wang G, Cao Y . Elevated serum levels of S100A8/A9 and HMGB1 at hospital admission are correlated with inferior clinical outcomes in COVID-19 patients. Cell Mol Immunol. 2020; 17(9):992-994. PMC: 7332851. DOI: 10.1038/s41423-020-0492-x. View

13.

Dasu M, Devaraj S, Park S, Jialal I . Increased toll-like receptor (TLR) activation and TLR ligands in recently diagnosed type 2 diabetic subjects. Diabetes Care. 2010; 33(4):861-8. PMC: 2845042. DOI: 10.2337/dc09-1799. View

14.

Sente T, Van Berendoncks A, Fransen E, Vrints C, Hoymans V . Tumor necrosis factor-α impairs adiponectin signalling, mitochondrial biogenesis, and myogenesis in primary human myotubes cultures. Am J Physiol Heart Circ Physiol. 2016; 310(9):H1164-75. DOI: 10.1152/ajpheart.00831.2015. View

15.

Harshman S, Shea M . The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis. Curr Nutr Rep. 2016; 5(2):90-98. PMC: 5026413. DOI: 10.1007/s13668-016-0162-x. View

16.

Yang H, Ochani M, Li J, Qiang X, Tanovic M, Harris H . Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci U S A. 2003; 101(1):296-301. PMC: 314179. DOI: 10.1073/pnas.2434651100. View

17.

Goddek S . Vitamin D3 and K2 and their potential contribution to reducing the COVID-19 mortality rate. Int J Infect Dis. 2020; 99:286-290. PMC: 7406600. DOI: 10.1016/j.ijid.2020.07.080. View

18.

Tomizawa A, Hattori Y, Kasai K, Nakano Y . Adiponectin induces NF-kappaB activation that leads to suppression of cytokine-induced NF-kappaB activation in vascular endothelial cells: globular adiponectin vs. high molecular weight adiponectin. Diab Vasc Dis Res. 2008; 5(2):123-7. DOI: 10.3132/dvdr.2008.020. View

19.

Yamauchi T, Iwabu M, Okada-Iwabu M, Kadowaki T . Adiponectin receptors: a review of their structure, function and how they work. Best Pract Res Clin Endocrinol Metab. 2014; 28(1):15-23. DOI: 10.1016/j.beem.2013.09.003. View

20.

Sente T, Van Berendoncks A, Hoymans V, Vrints C . Adiponectin resistance in skeletal muscle: pathophysiological implications in chronic heart failure. J Cachexia Sarcopenia Muscle. 2016; 7(3):261-74. PMC: 4864225. DOI: 10.1002/jcsm.12086. View