Monday, October 3, 2016

Fast-progression Type one diabetes and Slow-progression type one diabetes could be caused by different virus families

Autoimmune cross-targeting hypothesis:

Simultaneous infections on a target, one inside like a virus and one outside like a bacteria, triggers autoimmunity. In the case of type one diabetes two viral infection culprits are suspected as capable of triggering autoimmunity.

This post takes the hypothesis one step further and suggests that the trigger virus by using a specific type of receptor make a distinctive form of type one diabetes.  One that has characteristics linked to the receptor the virus used.

Acetylcholine receptors and enteroviruses (coxsackie, D68)

Dopamine receptors and flu viruses

If both of these viruses trigger type 1 diabetes through autoimmune cross-targeting are there actually two types of type 1 diabetes?

Dopamine D2-receptors when triggered inhibit insulin secretion
http://www.jbc.org/content/280/44/36824.long

Because the virus uses a receptor that when triggered inhibits insulin  immediately: flu may cause the "fast-type one diabetes"

Acetylcholine receptors when triggered increase insulin secretion (potentiating insulin release)
http://www.pathwaycommons.org/pc/record2.do?id=486085
http://www.reactome.org/content/detail/R-HSA-399997

acetylcholine receptor mutated mice showed impaired insulin release
https://www.ncbi.nlm.nih.gov/pubmed/15220195

enteroviruses and type 1 diabetes
https://www.ncbi.nlm.nih.gov/pubmed/17966045
https://www.ncbi.nlm.nih.gov/pubmed/16091441
https://www.ncbi.nlm.nih.gov/pubmed/20351698
http://www.healthline.com/health-news/could-enteroviruses-be-behind-type-1-diabetes-rising-rates-102214

HLA : these are the "mailboxes" your cells hold up to T cells to identify the viral infections inside

Slowly progressive form of type one diabetes linked to HLA-DR3
https://www.ncbi.nlm.nih.gov/pubmed/3486790

Coxsackie antibodies are increased in HLA-DR3 positive type one diabetes
https://www.ncbi.nlm.nih.gov/pubmed/12941542

This seems to support the enteroviruses cause the "slow-type one diabetes"

Further the groove in the HLA-4 seems to fit the flu proteins
https://www.ncbi.nlm.nih.gov/pubmed/16451200

note that HLA-3 and HLA-4 are the ones associated with type one diabetes
https://www.ncbi.nlm.nih.gov/pubmed/46642?dopt=Abstract















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