An updated computer model of Type 1 Diabetes Mellitus in neonatal patients.

In the original computer model (Fall 2021 NES 66,9 B01.00003) a mutant pathway of four steps leads to the demise of the pancreatic beta cell and permanent neonatal diabetes disease. The study focused on a DNA triplet involved in the translation of the preproinsulin precursor peptide mRNA into the mature bioactive insulin protein. Failure of this start codon to properly initiate the reading frame for the translation led to simulation model predictions of translocation defects. Variants such as truncated amino acid peptide chains, misfolded mutant proteins, severe cytosolic and ER stress, were all likely factors in the death of the host beta cell. The updated simulation has recently identified another factor.

 

The amino acid sequences (1 - 20) for normal and variant preproinsulin chains are:          

  normal - malwmrllpllallalwgpd    variant M1I - mrllpllallalwgpdpaaa

The variant chain is a self-derived antigen of the host reflecting the M1I mutation upstream. The sequence mrllpllallalwgpd is an epitope for this antigen (pone.0033884.s003). The Clostridiales (tetanus) family of bacteria (pone.0196551.s002) includes an identical pattern among its epitopes. The simulation will determine if similar epitopes of tetanus and diabetes antigens may interact to generate an incorrect auto-immune response with type 1 diabetes as the result. Could the powerful vaccine that protects against neonatal tetanus (NT) be involved? The CDC standard protocol for clostridium tetani begins at two months. We will explore such questions.