Update on Etiopathogenesis of Type 1 Diabetes (T1D): Emphasis on Part of Crosstalk of Gut Microbiome, Pancreatic Cells & Bystander Activation of Memory CD8+T Cells with Mitochondrial Melatonergic Pathway: Treatment Repercussions - A Narrative Review

Citation: Dr. Kulvinder Kochar Kaur, Dr. Gautam Nand Allahbadia, Dr. Mandeep Singh, "Update on Etiopathogenesis of Type 1 Diabetes (T1D): Emphasis on Part of Crosstalk of Gut Microbiome, Pancreatic Cells & Bystander Activation of Memory CD8+T Cells with Mitochondrial Melatonergic Pathway: Treatment Repercussions - A Narrative Review", Universal Library of Medical and Health Sciences, Volume 01, Issue 01.

Copyright: This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Origin of type 1 diabetes mellitus(T1D) takes place from the incapacity of pancreatic ß cells to generate enough insulin generally as sequelae of considerable pancreatic ß cells damage. T1D gets classified as an immune modulated disease. Nevertheless, the events which guide pancreatic ß cells apoptosis still need events to be estimated, causing incapacity of avoidance of continued cellular damage. Changes in the mitochondrial working is definitely the main pathophysiological event reinforcing pancreatic ß cells depletion in T1D. Akin to numerous medical disorders, it has become attractive in T1D, the part of the gut microbiome inclusive of crosstalk of the gut bacteria with the fungal infection Candida albicans. Gut dysbiosis along with gut permeability are intricately correlated with escalated circulating lipopolysaccharide (LPS) and repressed butyrate quantities, which may work in decontrolling immune reactions and systemic mitochondrial working. Here we have reviewed the wider available outcomes of T1D pathophysiology, emphasizing the significance of mitochondrial melatonergic pathways of pancreatic ß cells in the guiding of mitochondrial impairment. The repression of mitochondrial melatonin makes pancreatic ß cells predisposed to Oxidative stress(OS ) and impaired mitophagy; minimally modulated by elimination of melatonin‘s induction of the PTEN induced kinase (PINK1) , thus repressing mitophagy and escalating autoimmune correlated major histocompatibility complex (MHC)-1. The melatonin’s immediate precursor N-acetyl serotonin (NAS), portrays a BDNF)”; simulator through the activation of the BDNF receptor TrkB. Since both full length (TrkB-FL) & truncated( TrkB-T1) possess a substantially robust part in pancreatic ß cells working and survival , NAS, portrays one more perspective of melatonergic pathways germane for pancreatic ß cells damage in T1D. Integration of the mitochondrial melatonergic pathways in T1D pathophysiology incorporates broader earlier differing outcomes over pancreatic intercellular events. The repressed Akkermansia muciniphilia, Lactobacillus johnsonii, butyrate, and shikimate pathway, inclusive of bacteriophages aid besides pancreatic ß cells apoptosis, however further to the bystander activation of CD8+T cells, that enhances effector function and avoids their thymic deselection. The gut microbiome is a significant estimator of the mitochondrial impairment guiding pancreatic ß cells elimination and autoimmune actions obtained from cytotoxic CD8+T cells. This possesses considerable future scientific work and treatment repercussions.

Keywords: Type 1 Diabetes; N-Acetylserotonin; Melatonin; Pancreatic ß Cells; Gut Microbiome; Mitochondria; TrkB

https://doi.org/10.70315/uloap.ulmhs.2023.0101006