The Nuanced Role of NADPH in the Complex Landscape of Metabolic Disorders

1.Introduction

Nicotinamide adenine dinucleotide phosphate hydrogen (NADPH), also known as reduced coenzyme II, is a critical cofactor in cellular antioxidant systems and lipid synthesis, which links insulin resistance and ferroptosis of pancreatic β cells in the context of metabolic disorders such as diabetes mellitus, playing a central role in maintaining metabolic homeostasis.

2. Biological role of NADPH

NADPH functions as a coenzyme essential to cellular metabolism, playing pivotal roles in various critical biological processes, such as ROS scavenging, ROS production, fatty acid synthesis and cholesterol synthesis.
 

3. Biosynthetic pathway of NADPH

Cellular production of NADPH is facilitated through several pathways, including the pentose phosphate pathway, the citric acid cycle, and fatty acid metabolism. The dynamic equilibrium between NADPH synthesis and consumption is essential for preserving cellular redox balance and enabling a host of biosynthetic reactions.

4. The role of NADPH in insulin secretion from pancreatic β-Cells

Both redox reaction and metabolic signaling can modulate insulin secretion from pancreatic β-cells, where NADPH plays a central role. It can not only serves as a metabolic coupling factor, but also acts as a custodian of β-cell integrity, delicately managing the interplay between metabolic inputs and insulin output.

5. The interaction between insulin resistance and NADPH

A substantial body of evidence reveals that NADPH is critical for the regulation of oxidative stress and inflammatory responses, the main contributors to the pathogenesis of insulin resistance. Specifically, NADPH is implicated in ROS production via NOX and is also utilized in the synthesis of new fatty acids, which contributes to the development of insulin resistance, particularly in the context of obesity-induced chronic inflammation.

6. The impact of NADPH upon the ferroptosis in the context of diabetes

In pancreatic β cells, the elevated blood sugar and pro-inflammatory cytokines can trigger oxidative stress and iron accumulation to promote lipid peroxidation, thereby facilitating the ferroptosis. In return, the ferroptosis can reduce insulin secretion and beta cell mass, which is contributive to the progression of diabetes. 


In general, NADPH plays a dual role in ferroptosis. On the one hand, it can promote ROS generation via NOX. On the other hand, it can support antioxidant defense through glutathione regeneration. In the context of diabetes, NADPH may predominantly fuel processes leading to ferroptosis, mainly due to the enhanced activity and affinity of NOX, which however requires further research for verification.

7. Conclusion

NADPH has a critical role in the complex landscape of metabolic disorders, particularly insulin resistance and ferroptosis. Regulating NADPH-related pathways may open up new opportunities for the treatment of metabolic disorders.

Reference

Moon, Dong-Oh. “NADPH Dynamics: Linking Insulin Resistance and β-Cells Ferroptosis in Diabetes Mellitus.” International journal of molecular sciences vol. 25,1 342. 26 Dec. 2023, doi:10.3390/ijms25010342

Production advantages and features of BONTAC NADPH

BONTAC has rich R&D experience and advanced technology in the biosynthesis of NADPH. Bonzyme whole-enzymatic method is adopted, which is environmental-friendly, with no harmful solvent residues. The purity of NADPH can reach up to 95%, which is benefited from the exclusive Bonpure seven-step purification technology. BONTAC has self-owned factories and has obtained a number of international certifications, where high quality and stable supply of products can be ensured. BONTAC has four domestic and foreign NADPH patents, leading the industry.

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