Deciphering the link between Diabetes mellitus and SARS-CoV-2 infection through differential targeting of microRNAs in the human pancreas

Bhavya,; Pathak, Ekta; Mishra, Rajeev

doi:10.1007/s40618-021-01693-3

Cited by 14 publications

(12 citation statements)

References 108 publications

(94 reference statements)

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“…Emerging evidence indicates an intricate relationship between SARS-CoV-2 infection and multi-organ dysfunctions (MODs), which affects the lungs, heart, kidney, intestine, olfactory epithelium, liver, and pancreas [ 24 – 30 ]. Acute pancreatitis (AP) is an inflammation of the pancreas that results in local and systemic complications, as well as multiple organ malfunctions and damage over time [ 12 – 16 ].…”

Section: Resultsmentioning

confidence: 99%

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Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions

Pathak

Atri

Mishra

2022

Interdiscip Sci Comput Life Sci

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The SARS-CoV-2 infection affects the lungs, heart, kidney, intestine, olfactory epithelia, liver, and pancreas and brings forward multi-organ dysfunctions (MODs). However, mechanistic details of SARS-CoV-2-induced MODs are unclear. Here, we have investigated the role of pancreatic secretory proteins to mechanistically link COVID-19 with MODs using single-cell transcriptome analysis. Secretory proteins were identified using the Human Protein Atlas. Gene ontology, pathway, and disease enrichment analyses were used to highlight the role of upregulated pancreatic secretory proteins (secretome). We show that SARS-CoV-2 infection shifts the expression profile of pancreatic endocrine cells to acinar and ductal cell-specific profiles, resulting in increased expression of acinar and ductal cell-specific genes. Among all the secretory proteins, the upregulated expression of IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF was mainly associated with disease of diverse organs. Extensive literature and experimental evidence are used to validate the association of the upregulated pancreatic secretome with the coagulation cascade, complement activation, renin-angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of an upregulated secretome on multi-organ systems such as nervous, cardiovascular, immune, digestive, and urogenital systems. Our study provides evidence that an upregulated pancreatic secretome is a possible cause of SARS-CoV-2-induced MODs. This finding may have a significant impact on the clinical setting regarding the prevention of SARS-CoV-2-induced MODs. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s12539-022-00513-3.

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Section: Resultsmentioning

confidence: 99%

“…Several aspects of SARS-CoV-2-induced organ damage have been studied [ 24 – 30 ]. However, the involvement of specific pathways, such as those centred on pancreatic infection of SARS-CoV-2, needs to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions

Pathak

Atri

Mishra

2022

Interdiscip Sci Comput Life Sci

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“…Another study also found that dendritic cells, which are the “professional” IFN producing cells, are poor producers of INF-α in human diabetes [ 41 ]. Furthermore, Bhavya et al suggested that host microRNAs play a pivotal role in linking the diabetes and COVID-19 severity [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Shared genetic architecture between type 2 diabetes and COVID-19 severity

Qiu

Yin

et al. 2022

J Endocrinol Invest

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Purpose Patients with type 2 diabetes (T2D) have demonstrated a higher risk for developing more severe cases of COVID-19, but the complex genetic mechanism between them is still unknown. The aim of the present study was to untangle this relationship using genetically based approaches. Methods By leveraging large-scale genome-wide association study (GWAS) summary statistics of T2D and COVID-19 severity, linkage disequilibrium score regression and Mendelian randomization (MR) analyses were utilized to quantify the genetic correlations and causal relationships between the two traits. Gene-based association and enrichment analysis were further applied to identify putative functional pathways shared between T2D and COVID-19 severity. Results Significant, moderate genetic correlations were detected between T2D and COVID-19 hospitalization ( r g = 0.156, SE = 0.057, p = 0.005) or severe disease ( r g = 0.155, SE = 0.057, p = 0.006). MR analysis did not support evidence for a causal effect of T2D on COVID-19 hospitalization (OR 1.030, 95% CI 0.979, 1.084, p = 0.259) or severe disease (OR 0.999, 95% CI 0.934, 1.069, p = 0.982). Genes having p gene < 0.05 for both T2D and COVID-19 severe were significantly enriched for biological pathways, such as response to type I interferon, glutathione derivative metabolic process and glutathione derivative biosynthetic process. Conclusions Our findings further confirm the comorbidity of T2D and COVID-19 severity, but a non-causal impact of T2D on severe COVID-19. Shared genetically modulated molecular mechanisms underlying the co-occurrence of the two disorders are crucial for identifying therapeutic targets. Supplementary Information The online version contains supplementary material available at 10.1007/s40618-022-01920-5.

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“…Common pathogenetic processes between COVID‐19 and diabetes mellitus discovered by differential gene expressions pattern analysis are related to the mRNA metabolism, subcellular organelle organization, nucleotide synthesis, immune responses, and autophagy process. Other studies revealed that five biomarker genes ( CP , SOCS3 , AGT , PSMB8 , and CFB ) and 4 miRNAs (hsa‐miR‐298, hsa‐miR‐3925‐5p, hsa‐miR‐4691‐3p, and hsa‐miR‐5196‐5p) closely bridge T2DM and COVID‐19 585–587 …”

Section: Therapeutic Targets In T2dm Complicationsmentioning

confidence: 99%

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

Cao

Tian

Zhang

et al. 2023

MedComm

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Type 2 diabetes mellitus (T2DM) represents one of the fastest growing epidemic metabolic disorders worldwide and is a strong contributor for a broad range of comorbidities, including vascular, visual, neurological, kidney, and liver diseases. Moreover, recent data suggest a mutual interplay between T2DM and Corona Virus Disease 2019 (COVID‐19). T2DM is characterized by insulin resistance (IR) and pancreatic β cell dysfunction. Pioneering discoveries throughout the past few decades have established notable links between signaling pathways and T2DM pathogenesis and therapy. Importantly, a number of signaling pathways substantially control the advancement of core pathological changes in T2DM, including IR and β cell dysfunction, as well as additional pathogenic disturbances. Accordingly, an improved understanding of these signaling pathways sheds light on tractable targets and strategies for developing and repurposing critical therapies to treat T2DM and its complications. In this review, we provide a brief overview of the history of T2DM and signaling pathways, and offer a systematic update on the role and mechanism of key signaling pathways underlying the onset, development, and progression of T2DM. In this content, we also summarize current therapeutic drugs/agents associated with signaling pathways for the treatment of T2DM and its complications, and discuss some implications and directions to the future of this field.

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Deciphering the link between Diabetes mellitus and SARS-CoV-2 infection through differential targeting of microRNAs in the human pancreas

Cited by 14 publications

References 108 publications

Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions

Single-Cell Transcriptome Analysis Reveals the Role of Pancreatic Secretome in COVID-19 Associated Multi-organ Dysfunctions

Shared genetic architecture between type 2 diabetes and COVID-19 severity

Signaling pathways and intervention for therapy of type 2 diabetes mellitus

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