Cell subjournal: Altering the transport of glucagon receptors in the liver can regulate its metabolic signaling

A team of researchers from the Helmholtz Munich Institute for Diabetes and Cancer Research (IDC) and the German Diabetes Research Center (DZD) have revealed a new strategy
to alter glucagon receptor signaling in the liver by altering intracellular transport.
Glucagon is a peptide hormone responsible for blood sugar balance, which regulates blood sugar levels
.
This new approach offers therapeutic potential
for the treatment of type 2 diabetes by decoupling glucagon's glucose and lipid metabolism-related effects.

During fasting, the hormone glucagon circulates in the body, initiating the release and breakdown of glucose and lipids stored by the liver to provide energy
.
Until now, it is unclear whether and how the use of these two energy sources (glucose and lipids) is activated
independently.
A study by Revathi Sekar, Karsten Motzler and colleagues found that consuming the protein Vps37a from the liver altered the localization of intracellular glucagon receptors, thereby activating glucose metabolism
on the inner cell membrane without affecting lipids.

VPS37A controls the transport of glucagon receptors in cells

The liver is the main organ that maintains the balance of fasting blood sugar levels, and it releases stored glucose
through external signals such as glucagon.
However, in type 2 diabetes, this pathway is overactivated, causing the liver to produce glucose, despite already high
blood sugar levels.
This condition in which the level of glucose in the blood is too high is called hyperglycemia
.
Pharmacological inhibition of the action of glucagon in the liver has proven challenging because glucagon not only regulates glucose production but also mediates the breakdown
of lipids in the liver.
Thus, blocking the glucagon action has a negative effect
on the accumulation of lipids in the liver.
The research team, led by Dr.
Anja Zeigerer, team leader at the International Data Center, has now found a possible way to break off both pathways by interfering with intracellular localization and signaling pathways of glucagon receptors, thereby restoring glucagon antagonists as a potential treatment for
type 2 diabetes.

New treatment options are needed

The prevalence of obesity and related type 2 diabetes is increasing
significantly.
However, because not every patient responds equally well to existing therapies, more treatment options
are needed.
The study by first authors Revathi Sekar and Karsten Motzler and colleagues expands the current therapeutic range
by providing a good way to effectively lower blood sugar by inhibiting glucagon without developing lipid-related side effects.