Related Experiment Video

Updated: Dec 4, 2025

Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets
09:31

Assessing Replication and Beta Cell Function in Adenovirally-transduced Isolated Rodent Islets

Published on: June 25, 2012

14.3K

Inhibition of oxidative metabolism by nitric oxide restricts EMCV replication selectively in pancreatic beta-cells

Joshua D Stafford1, Chay Teng Yeo1, John A Corbett1

  • 1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.

The Journal of Biological Chemistry
|October 26, 2020
PubMed

Insights

Viral infections can trigger autoimmune diabetes. Nitric oxide protects beta cells from encephalomyocarditis virus (EMCV) by targeting metabolic pathways essential for insulin secretion, preventing cell death.

Area of Science:

  • Immunology
  • Virology
  • Metabolic research

Background:

  • Environmental factors, including viral infections, are implicated in autoimmune diabetes development.
  • Encephalomyocarditis virus (EMCV) infection of pancreatic islet cells triggers inflammation via macrophage-derived IL-1β.
  • Nitric oxide (NO) produced by beta cells inhibits EMCV replication and lysis, linked to altered mitochondrial metabolism.

Purpose of the Study:

  • To investigate the protective mechanisms of nitric oxide against EMCV infection in beta cells.
  • To determine if NO-mediated protection is selective for beta cells and linked to metabolic coupling.
  • To explore the role of mitochondrial metabolism in beta cell susceptibility to viral infection.

Main Methods:

  • Utilized EMCV infection models in beta cells and mouse embryonic fibroblasts (MEFs).
  • Assessed the effects of nitric oxide and mitochondrial respiration inhibitors on viral replication and ATP levels.
  • Analyzed the metabolic coupling between glycolysis and mitochondrial oxidation in response to NO.

Main Results:

  • Nitric oxide's protective effects against EMCV are specific to beta cells.
  • NO-mediated protection involves metabolic coupling necessary for insulin secretion.
  • Inhibition of mitochondrial respiration reduces EMCV replication and ATP levels in beta cells, but not in MEFs unless they are forced to rely on oxidative metabolism.

Conclusions:

  • Nitric oxide selectively targets metabolic pathways crucial for glucose-stimulated insulin secretion in beta cells to confer protection against EMCV.
  • Beta cell metabolism is uniquely vulnerable to EMCV, and NO exploits this vulnerability for defense.
  • Understanding these beta cell-specific metabolic adaptations is key to developing strategies against viral-induced autoimmune diabetes.
Keywords:
EMCVautoimmune diabetesbeta celldiabetesglucose metabolisminnate immunitymitochondriamitochondrial metabolismnitric oxideplus-stranded RNA virusvirus replicationβ-cells

More Related Videos

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds12:32

High-resolution Respirometry to Measure Mitochondrial Function of Intact Beta Cells in the Presence of Natural Compounds

Published on: January 23, 2018

12.7K
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals07:39

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals

Published on: June 25, 2018

7.6K

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
5.4K
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
89.3K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
17.5K
The Electron Transport Chain01:30

The Electron Transport Chain

The electron transport chain or oxidative phosphorylation is an exothermic process in which free energy released during electron transfer reactions is coupled to ATP synthesis. This process is a significant source of energy in aerobic cells, and therefore inhibitors of the electron transport chain can be detrimental to the cell's metabolic processes.
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
19.0K
Glucose Homeostasis: Pancreatic Islets and Insulin Secretion01:27

Glucose Homeostasis: Pancreatic Islets and Insulin Secretion

The pancreatic islets comprising only 1%-2% of the volume are highly vascularized and innervated mini-organs. They contain five endocrine cell types, including β cells that secrete insulin, which is synthesized as a single polypeptide chain, preproinsulin, processed to proinsulin, and finally to insulin and C-peptide. This process is complex and regulated, involving the Golgi complex, the endoplasmic reticulum, and the secretory granules of the β cell.
Insulin and C-peptide are...
1.9K