bioelectrics revisited: part 2

A lifelong solution to T1D – could it be true?

T1D patients’ lives have dramatically improved with the introduction of closed-loop hybrid systems integrating CGM (continuous glucose monitoring) with micro-needle insulin pumps, which together are referred to as artificial pancreases (AP). While restrictive diets and finger pricks prevail no longer, SMBG (self-monitoring of blood glucose) and sometimes fatal side-effects still exist. While the AP replaces the beta-cells’ functions entirely, new developments in stem cell-derived beta clusters show an even more promising treatment that involves fully integrated biocircuits.  Let’s take a look at how this could work. 

On its own, stem cell-derived beta-cell replacement therapy lacks key connections to the parasympathetic nervous system. You see, endogenous beta-cells in the pancreas are innervated by vagal efferent fibers which help regulate b-cells’ insulin release. How does this circuit work?

  • When the beta-cells release insulin, serotonin is co-released to convey information specifically to the nerve fibers.
  • The fibers’ nerve terminals have serotonin receptors that pick up on the amount of serotonin released — so the brain is kept updated on the amount of insulin being secreted.
  • Depending on the info it receives, the brain sends back a signal through the afferent vagal nerve fibers and releases a certain amount of acetylcholine (ACh) .
  • The ACh is used to help make the B-cells more effective in response to glucose.

Power to the light

A recent study uses optogenetic stimulation to offer evidence that this glycemic control circuit really does work.

  • A mouse model expressed ChannelRhodopsin2 (ChR2) in vagal parasympathetic neurons that innervate pancreatic beta-cells.
  • Light activated these neurons at their terminals in the pancreas as well as at their axons of the cervical vagus nerve.
  • In both cases, light-activation caused increases in plasma insulin and blood flow as well as a rapid reduction of blood glucose.

The big picture: Biocircuit-controlled, functional living tissue implants could incorporate these endogenous innervations to restore normal modulation functions of beta-cell secretion, as well as a whole lot of other advantages. Namely, a life-long solution to T1D.

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