Bi-hormonal dysfunction in both type 1 and 2 diabetes

This is sort of a continuation of @MsCris thread -

What got me my attention again was reading about the iLet pump that is in the investigative phase of FDA approval. There is the possibility of this becoming a dual pump able to infuse insulin and glucagon as determined by a CGM sensor. The iLet article mentioned that it is a known thing that type 1s have dysfunctional Alpha cell response. I was thinking this because my T1DM friends I know in the flesh as well as in forums like this seem to have poor natural response to low blood glucose levels. I found a good paper on this bi-hormonal disjunction in T1DMs - Mini‐review: Glucagon responses in type 1 diabetes – a matter of complexity - PMC
So, I guess I have too much time on my hands. This got me thinking about my sub-tribe, T2DM, especially those like me who are know on MDI/pump because of Beta cell decline. I didn’t find anything that addressed that in particular, but this paper on T2DM in general and how glucagon secretion is out of whack - secreting at the wrong time and not at the right time.
The interplay of all the body’s hormones is so very complex.


I was thinking the same thing in the thread about glucagon - that it seems pretty complex to create a semi automatic system with something like a Tandem control-iq, but that it would be even more complex to have a system providing glucagon as well as insulin. Maybe the software is too complicated …


One thing that a dual hormone pump would not be able to replicate is the interaction between the various cells in the islets. Alpha cells have insulin receptors and Beta cells have glucagon receptors. These receptors only respond to hormones within the islets, if I understand correctly. It is a negative feedback system to keep things balanced.

Exogenic delivery of insulin and glucagon will not have this biological control systems. It would rely on blood glucose sensors and have to sense the need to decrease insulin when glycagon is being infused and vise versa.

I suspect that this idea is not ready for prime time yet.

The following paper explores the complexities of cell interaction within the islets. Also issues with dysfunctional communication is transplanted islets. Not all the interaction between the 4 cells and the 6 hormones secreted has been explored in depth or at all. This paper focuses on the alpha, beta and delta cells.

I wonder about amylin long discounted as unnecessary, but now gaining some interest and the stepchild biochemical - C-Peptide. There may be something that C-Peptide is good for other than determining endocrine insulin secretion.
Below is an image from the paper- below that a link to the paper.

There is a lot more in this paper than they little that caught my attention.