Rigorous dissection of the signaling mechanisms and circuits underlying GLP1R agonist weight loss effects mice. Huge achievement by Claire Gao and team @mikekrashes.bsky.social. Potential avenues for harnessing complexity of signaling to create novel treatments. www.biorxiv.org/content/10.1...
Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons
Glucagon-like peptide 1 receptor (GLP1R) agonists like semaglutide drive weight loss through the brain, but insights into their intracellular signaling mechanisms are lacking. Although canonically GLP...
www.biorxiv.org
August 17, 2025 at 12:31 AM
Rigorous dissection of the signaling mechanisms and circuits underlying GLP1R agonist weight loss effects mice. Huge achievement by Claire Gao and team @mikekrashes.bsky.social. Potential avenues for harnessing complexity of signaling to create novel treatments. www.biorxiv.org/content/10.1...
By running a GWAS on data we collected from an online survey about GLP-1 medication, we found a missense variant in GLP1R that predicts treatment success. This makes sense! GLP1R is the target of the GLP-1 medications!
April 8, 2026 at 3:42 PM
By running a GWAS on data we collected from an online survey about GLP-1 medication, we found a missense variant in GLP1R that predicts treatment success. This makes sense! GLP1R is the target of the GLP-1 medications!
Has anyone looked at whether you could "re-discover" GLP1R as a key gene from BMI or T2D GWAS? Or does it look pretty typical?
December 31, 2024 at 7:47 PM
Has anyone looked at whether you could "re-discover" GLP1R as a key gene from BMI or T2D GWAS? Or does it look pretty typical?
Nature research paper: A brain reward circuit inhibited by next-generation weight-loss drugs in mice
go.nature.com/4uuw7ti
go.nature.com/4uuw7ti
A brain reward circuit inhibited by next-generation weight-loss drugs in mice - Nature
Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implications for how these orally delivered weight-loss drugs engage brain reward circuits.
go.nature.com
May 12, 2026 at 10:27 AM
Nature research paper: A brain reward circuit inhibited by next-generation weight-loss drugs in mice
go.nature.com/4uuw7ti
go.nature.com/4uuw7ti
#GLP1R #Pericyte
GLP1R agonist (Exendin-4) relaxes cardiac #Pericyte & dilates constricted capillaries in oxygen-glucose-derived perfused🐭right ventricle wall
A role of KATP channel Kir6.1
bioRxiv 2025
www.biorxiv.org/content/10.1...
GLP1R agonist (Exendin-4) relaxes cardiac #Pericyte & dilates constricted capillaries in oxygen-glucose-derived perfused🐭right ventricle wall
A role of KATP channel Kir6.1
bioRxiv 2025
www.biorxiv.org/content/10.1...
July 16, 2025 at 11:22 AM
#GLP1R #Pericyte
GLP1R agonist (Exendin-4) relaxes cardiac #Pericyte & dilates constricted capillaries in oxygen-glucose-derived perfused🐭right ventricle wall
A role of KATP channel Kir6.1
bioRxiv 2025
www.biorxiv.org/content/10.1...
GLP1R agonist (Exendin-4) relaxes cardiac #Pericyte & dilates constricted capillaries in oxygen-glucose-derived perfused🐭right ventricle wall
A role of KATP channel Kir6.1
bioRxiv 2025
www.biorxiv.org/content/10.1...
Studies in cells and mice reveal that the human GLP1R A316T variant exhibits characteristics of constitutive activation but dampened GLP-1RA responses www.science.org/doi/10.1126/...
In vivo functional profiling and structural characterization of the human GLP1R A316T variant
The GLP1R A316T missense variant displays improved glucose tolerance but impaired pharmacological incretin responses in vivo.
www.science.org
February 4, 2026 at 9:22 PM
Studies in cells and mice reveal that the human GLP1R A316T variant exhibits characteristics of constitutive activation but dampened GLP-1RA responses www.science.org/doi/10.1126/...
Genetic variants in GLP1R and GIPR, which encode targets of GLP-1-based medications, offer insights into why responses to these drugs vary and who might face adverse effects
go.nature.com/4vBzAYy
go.nature.com/4vBzAYy
Genetics reveal why people respond differently to GLP-1 weight-loss drugs
Genetic variants in GLP1R and GIPR, which encode targets of GLP-1-based medications, offer insights into why responses to these drugs vary and who might face adverse effects.
go.nature.com
April 13, 2026 at 1:04 PM
Genetic variants in GLP1R and GIPR, which encode targets of GLP-1-based medications, offer insights into why responses to these drugs vary and who might face adverse effects
go.nature.com/4vBzAYy
go.nature.com/4vBzAYy
This time we found variants in both GLP1R and GIPR associated with nausea and vomiting. Interestingly, the GIPR association was specific to patients taking tirzepatide (aka Mounjaro or Zepbound)... this also makes sense; tirzepatide targets both GLP1R and GIPR!
April 8, 2026 at 3:42 PM
This time we found variants in both GLP1R and GIPR associated with nausea and vomiting. Interestingly, the GIPR association was specific to patients taking tirzepatide (aka Mounjaro or Zepbound)... this also makes sense; tirzepatide targets both GLP1R and GIPR!
Now in peer-reviewed form: www.nature.com/articles/s41...
A brain reward circuit inhibited by next-generation weight-loss drugs in mice - Nature
Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implicati...
www.nature.com
May 6, 2026 at 10:13 PM
Now in peer-reviewed form: www.nature.com/articles/s41...
Awesome work by @aguler.bsky.social and team providing critical new insights into the mechanisms of next-gen (small molecule) GLP-1R agonists!!!! Turns out the CeA is important :)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
A brain reward circuit inhibited by next-generation weight-loss drugs in mice - Nature
Humanized glucagon-like peptide 1 receptor (GLP1R) mouse models are used to investigate the neural circuitry through which small-molecule GLP1R agonists modulate feeding, with implicati...
www.nature.com
May 6, 2026 at 4:12 PM
Awesome work by @aguler.bsky.social and team providing critical new insights into the mechanisms of next-gen (small molecule) GLP-1R agonists!!!! Turns out the CeA is important :)
www.nature.com/articles/s41...
www.nature.com/articles/s41...
Check out this cool preprint from the Krashes and Lutas labs on the signaling mechanisms of semaglutide GLP-1R agonism in the dorsal vagal complex:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons
Glucagon-like peptide 1 receptor (GLP1R) agonists like semaglutide drive weight loss through the brain, but insights into their intracellular signaling mechanisms are lacking. Although canonically GLP...
www.biorxiv.org
September 10, 2025 at 3:02 PM
Check out this cool preprint from the Krashes and Lutas labs on the signaling mechanisms of semaglutide GLP-1R agonism in the dorsal vagal complex:
www.biorxiv.org/content/10.1...
www.biorxiv.org/content/10.1...
GPCRvp, a GPCR-specific variant impact predictor, decodes GLP1R missense variants using molecular dynamics + AI. It sharply reduces false positives vs AlphaMissense and improves prediction of GLP 1 drug response. #GLP1R #GPCR #Diabetes #Obesity link.springer.com/article/10.1... 🔓
The GPCRVP score reliably predicts the impact of GLP1R human variants on receptor function - Diabetologia
Aims/hypothesis The glucagon-like peptide-1 receptor (GLP1R) is a key regulator of glucose homeostasis and body weight, and a major therapeutic target for type 2 diabetes and obesity. Individual disea...
link.springer.com
September 25, 2026 at 12:34 PM
GPCRvp, a GPCR-specific variant impact predictor, decodes GLP1R missense variants using molecular dynamics + AI. It sharply reduces false positives vs AlphaMissense and improves prediction of GLP 1 drug response. #GLP1R #GPCR #Diabetes #Obesity link.springer.com/article/10.1... 🔓
Our work on cAMP-dependent mechanisms in area postrema that mediate Semaglutide-induced weight loss in mice is out in final form. I learned a lot from this study and the effort of the team, especially Claire Gao who led the work, was inspiring. I hope it can stimulate new directions.
rdcu.be/fj8Eu
rdcu.be/fj8Eu
Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons
Nature Metabolism - Semaglutide-induced weight loss is shown to depend on Gs-coupled signalling in GLP1R-expressing hindbrain neurons, with a critical role for cAMP in mediating neuronal activation...
rdcu.be
May 25, 2026 at 6:00 PM
Our work on cAMP-dependent mechanisms in area postrema that mediate Semaglutide-induced weight loss in mice is out in final form. I learned a lot from this study and the effort of the team, especially Claire Gao who led the work, was inspiring. I hope it can stimulate new directions.
rdcu.be/fj8Eu
rdcu.be/fj8Eu
LUXendin 492/551/555/615/645/651/762
Fluorescent Exendin4(9–39)
Visualize membrane #GLP1R in fixed/live cell & animals (retro-orbital or s.c. injection)
Also act as GLP1R antagonists
Are pancreatic Pericytes also labeled!?😍
#JACSAu 2022
pubs.acs.org/doi/10.1021/...
Fluorescent Exendin4(9–39)
Visualize membrane #GLP1R in fixed/live cell & animals (retro-orbital or s.c. injection)
Also act as GLP1R antagonists
Are pancreatic Pericytes also labeled!?😍
#JACSAu 2022
pubs.acs.org/doi/10.1021/...
July 14, 2025 at 7:00 PM
LUXendin 492/551/555/615/645/651/762
Fluorescent Exendin4(9–39)
Visualize membrane #GLP1R in fixed/live cell & animals (retro-orbital or s.c. injection)
Also act as GLP1R antagonists
Are pancreatic Pericytes also labeled!?😍
#JACSAu 2022
pubs.acs.org/doi/10.1021/...
Fluorescent Exendin4(9–39)
Visualize membrane #GLP1R in fixed/live cell & animals (retro-orbital or s.c. injection)
Also act as GLP1R antagonists
Are pancreatic Pericytes also labeled!?😍
#JACSAu 2022
pubs.acs.org/doi/10.1021/...
This is a reasonable summary but I have concerns. Anaesthetists are worried and I'm not sure they're being listened to.
A response:
www.linkedin.com/posts/abhijo...
A response:
www.linkedin.com/posts/abhijo...
February 3, 2025 at 10:00 AM
This is a reasonable summary but I have concerns. Anaesthetists are worried and I'm not sure they're being listened to.
A response:
www.linkedin.com/posts/abhijo...
A response:
www.linkedin.com/posts/abhijo...
Now: Dmitry Shungin: Comprehensive Proteomic Characterization of GLP1R Therapy: Leveraging Mendelian Randomization and Colocalization with Validation in Clinical Trials #ASHG25 🧪🧬🖥️
PheedLoop
meetings.ashg.org
October 14, 2025 at 9:25 PM
Now: Dmitry Shungin: Comprehensive Proteomic Characterization of GLP1R Therapy: Leveraging Mendelian Randomization and Colocalization with Validation in Clinical Trials #ASHG25 🧪🧬🖥️
Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons https://www.biorxiv.org/content/10.1101/2025.08.12.668772v1
August 16, 2025 at 3:15 AM
Semaglutide drives weight loss through cAMP-dependent mechanisms in GLP1R-expressing hindbrain neurons https://www.biorxiv.org/content/10.1101/2025.08.12.668772v1
P2 #weightloss data over 13 weeks for VK2735 the once weekly GIPR-GLP1R medicine in adults with #obesity or overweight and ≥ 1 weight-related comorbidity onlinelibrary.wiley.com/doi/10.1002/...
January 10, 2026 at 12:29 PM
P2 #weightloss data over 13 weeks for VK2735 the once weekly GIPR-GLP1R medicine in adults with #obesity or overweight and ≥ 1 weight-related comorbidity onlinelibrary.wiley.com/doi/10.1002/...
🧠🍽️ Glp1r-Lepr coexpressing neurons in the dorsomedial hypothalamus modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist
🔗 www.science.org/doi/10.1126/...
#ingestivebehavior #weightloss #neuroskyence
🔗 www.science.org/doi/10.1126/...
#ingestivebehavior #weightloss #neuroskyence
Glp1r-Lepr coexpressing neurons modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist
Orthogonal murine models demonstrate the bioactivity and neuronal targets of a GLP-1/leptin coagonist in relation to food intake and body weight.
www.science.org
December 10, 2024 at 8:56 AM
🧠🍽️ Glp1r-Lepr coexpressing neurons in the dorsomedial hypothalamus modulate the suppression of food intake and body weight by a GLP-1/leptin dual agonist
🔗 www.science.org/doi/10.1126/...
#ingestivebehavior #weightloss #neuroskyence
🔗 www.science.org/doi/10.1126/...
#ingestivebehavior #weightloss #neuroskyence
Excellent review including all the available data and pharmacology of commonly used drugs and breastfeeding in @kireports.bsky.social
www.kireports.org/article/S246...
#NephSky
1/2
www.kireports.org/article/S246...
#NephSky
1/2
May 5, 2025 at 1:56 PM
Excellent review including all the available data and pharmacology of commonly used drugs and breastfeeding in @kireports.bsky.social
www.kireports.org/article/S246...
#NephSky
1/2
www.kireports.org/article/S246...
#NephSky
1/2
New work stemming from an amazing collaboration with @addisonwebster0 and @AUGCsoup using a combination of rabies mapping and single cell sequencing to identify a GLP1R-expressing local input to AgRP cells that curbs appetite rdcu.be/d2gB5
Molecular connectomics reveals a glucagon-like peptide 1-sensitive neural circuit for satiety
Nature Metabolism - Combining rabies-based connectomics with single-nucleus transcriptomics, the authors identify a neural circuit through which GLP-1 receptor agonists suppress appetite in mice.
rdcu.be
December 3, 2024 at 1:40 PM
New work stemming from an amazing collaboration with @addisonwebster0 and @AUGCsoup using a combination of rabies mapping and single cell sequencing to identify a GLP1R-expressing local input to AgRP cells that curbs appetite rdcu.be/d2gB5