Diabetes is a chronic condition characterized by prolonged high blood glucose levels due to the body’s insulin resistance or inability to produce the hormone. Worldwide, more than 425 Million people are victims of this disease and are expected to increase by another 200 Million within the next two decades. Neuropathy is characterized by damage or dysfunction of the nerves. Diabetic neuropathy (DN) is the amalgamation of diabetes and nerve damage where the former acts as a causative for the latter. It is estimated that about 50% of all diabetics are prone to develop DN.
How?
Some of the more studied molecular mechanisms include;
Ø Formation of Advanced Glycation End products (AGEs): Advanced Glycation End products are Biomolecules formed in the body by the non-enzymatic glycation of protein or lipid molecules with reducing sugars
Ø Oxidative stress caused due to increased formation of Reactive Oxygen Species (ROS): Reactive Oxygen Species are highly reactive molecules formed from diatomic Oxygen
Ø Neuro-signaling disruption due to the production of pro-inflammatory cytokines
Ø Release of apoptotic factors by mitochondrial dysfunction caused by osmotic stress
How do AGEs lead to DN?
1. AGEs are directly responsible for the generation of ROS by the activation of NADPH oxidase enzymes.
2. NADPH Oxidase generates superoxide radicals as a result of their enzymatic activity of transferring an electron from NADPH to O2 leading to the formation of NADP+ and O2-, which is a ROS.
3. These ROS further promote immune cell activation leading to increased production of pro-inflammatory cytokines such as TNF-α.
4. Pro-inflammatory cytokines significantly alter the K+ and Na+ ion transport channels in the cells causing significant osmotic stress responsible for mitochondrial and cell dysfunction
5. Mitochondria then releases pro-apoptotic factors leading to programmed cell death.
AGEs induced apoptosis - Mechanism of action
How does a dysfunction of nerve cells manifest physiologically?
Ø Feeling tingling, numbness and pain
Ø Loss of sensitivity and coordination
Ø Weakening of muscles
Ø Changes in blood pressure and heart rate
Ø Autonomic dysfunction
How severe is it?
Prolonged cases of diabetes could lead to severe cases of diabetic neuropathy characterized by severe disability, foot ulcers, infections and significant impairment in one’s quality of life.
How does one prevent DN?
Ø Regulation and maintenance of blood sugar levels
Ø Regular physical activity for enhancing body insulin sensitivity and blood circulation
Ø Controlled and healthy diet
References
Feldman EL;Callaghan BC;Pop-Busui R;Zochodne DW;Wright DE;Bennett DL;BrilV;Russell JW;Viswanathan V; Diabetic neuropathy [Internet]. U.S. National Library of Medicine; [cited 2023 Jun 2]. Available from: https://pubmed.ncbi.nlm.nih.gov/31197153/
Papachristou S, Pafili K, Papanas N. Skin ages and diabetic neuropathy - BMC endocrine disorders [Internet]. BioMed Central; 2021 [cited 2023 Jun 2]. Available from: https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-021-00697-7
Figueroa-Romero C, Sadidi M, Feldman EL. Mechanisms of disease: The oxidative stress theory of diabetic neuropathy - reviews in endocrine and metabolic disorders [Internet]. Springer US; 2008 [cited 2023 Jun 2]. Available from: https://link.springer.com/article/10.1007/s11154-008-9104-2
M; R-SD-NV. Role of inflammation in the pathogenesis of diabetic peripheral neuropathy [Internet]. U.S. National Library of Medicine; [cited 2023 Jun 2]. Available from: https://pubmed.ncbi.nlm.nih.gov/31592273/
R; YSS. Pathology and pathogenetic mechanisms of diabetic neuropathy: Correlation with clinical signs and symptoms [Internet]. U.S. National Library of Medicine; [cited 2023 Jun 2]. Available from: https://pubmed.ncbi.nlm.nih.gov/17462777/
By
V. Srinivasa Ragavan
Intern, Hexacara BioSolutions
nice info!
Useful one!!