How GLP-1 Drugs Affect Gene Expression

…and other items from this week’s health news:

GLP-1 receptor agonists affect more than we knew

Normally, short-lived hormonal signals trigger a quick response and then fade. Synthetic GLP-1 agonists remain in the body much longer than the natural hormone whose receptor’s they’re sneakily agonizing (sounds bad, but in this context it’s good), allowing sustained activation of gene programs.

How exactly? It increases signaling, which ultimately leads to phosphorylation of the Med14 protein within the Mediator transcription complex.

That’s a lot of big words, so to simplify a little: the Mediator complex controls large sets of genes rather than a single pathway, so activating Med14 can switch on broad gene programs that reshape how cells function over time.

Researchers (Dr. Sam Van de Velde et al.) examined the practical side of this, and found for example that in pancreatic beta cells, the result is improved stress resistance, greater survival, and enhanced insulin production, which helps counter metabolic syndrome, and its associated more specific maladies such as type 2 diabetes, heart disease of various kinds, etc.

And because these processes (per the Med14 switch etc) can occur in many different kinds of tissue, similar gene-expression changes may be occuring in the heart, brain, blood vessels, and fat tissue—but more research will be needed to confirm that, of course.

Read in full: How do GLP-1 agonists affect gene expression?

Related: Demystifying Peptides ← remember that GLP-1 is a peptide! GLP stands for “glucagon-like peptide”, and we talk about peptides’ effects on gene expression here too

The schizophrenia biomarker hiding in your cheek

Schizophrenia currently has no single definitive laboratory test, so clinicians rely mainly on observing symptoms such as hallucinations, delusions, and disorganized thinking, which can delay diagnosis for months, not to mention leave a lot of room for subjectivity on the part of the clinician.

However, researchers (Dr. Christen Crosta et al.) compared cheek-swab samples from 27 people with schizophrenia and 27 matched healthy controls, and found that patients with schizophrenia showed significantly higher activity of the Sp4 gene, which is involved in brain development and whose elevated expression correlated with more severe symptoms such as hallucinations and delusions.

Dr. Crosta and her team also found that schizophrenic patients had higher levels of the protein HSP60, which appears to be regulated by Sp4 and may act as a sort of “downstream” biological indicator of schizophrenia.

In short, if confirmed in larger studies, a simple cheek swab could help detect schizophrenia earlier or monitor disease progression in a fast and non-invasive way.

Read in full: Cheek cells may provide clues to schizophrenia risk

Related: The Disordered Mind – by Dr. Eric Kandel

A spray-on immune shield has been developed!

Organ transplant recipients usually take immunosuppressants to prevent rejection, but these drugs weaken the entire immune system (thus leaving the patient very vulnerable to infections; it’s a lot like giving someone a slightly weaker form of AIDS) and also can cause complications such as kidney toxicity.

So, it’s not great. Better than not having the organ in question, of course, but not great.

However! Researchers (Dr. Hyung Joon Cha et al.) have developed microscopic gel particles containing immunosuppressants that stick to organ surfaces using adhesive proteins inspired by mussels’ ability to cling to wet surfaces.

In other words: the sprayed microgels form an invisible layer on the organ that remains attached to the wet tissue and slowly releases the drug locally at the transplant site.

And, it worked! Because the medication stays mainly on the transplanted organ rather than circulating through the bloodstream, this approach is able to suppress rejection while minimizing whole-body side effects.

Read in full: Spray-on “immune-shield” coats transplant organs to curb rejection

Related: Rapamycin Can Slow Aging By 20% (But Watch Out) ← an alternative immunosuppressant

Take care!