GLP‐1 signals via ERK in peripheral nerve and prevents nerve dysfunction in diabetic mice
Open accessAbstract
Aim: Glucagon‐like peptide‐1 (GLP‐1) is an incretin hormone that induces glucose‐dependent insulin secretion and may have neurotrophic properties. Our aim was to identify the presence and activity of GLP‐1 receptors (GLP‐1Rs) in peripheral nerve and to assess the impact of GLP‐1R agonists on diabetes‐induced nerve disorders. Methods: Tissues were collected from streptozotocin‐diabetic rats. GLP‐1R function was assessed by incubating tissues from normal and diabetic rats with GLP‐1R agonists and antagonists and measuring induction of ERK1/2 phosphorylation by Western blot. Streptozotocin‐diabetic mice were also treated with the GLP‐1R agonist exenatide for 8 weeks to assess the impact of GLP‐1R signalling on peripheral nerve function and structure. Results: GLP‐1R protein was detected in rat dorsal root ganglia and the neurons and Schwann cells of the sciatic nerve. Protein levels were not affected by streptozotocin‐induced diabetes. GLP‐1R agonists did not signal via ERK1/2 in sciatic nerve of normal rats. However, GLP‐1R agonists significantly increased pERK1/2 levels in sciatic nerves from diabetic rats, indicating that GLP‐1Rs are functional in this tissue. Exenatide treatment did not affect blood sugar, insulin levels or paw thermal response latencies in either control or diabetic mice. However, the reductions of motor nerve conduction velocity and paw intraepidermal fibre density seen in diabetic mice were attenuated by exenatide treatment. Conclusions: These data show that the peripheral nerve of diabetic rodents exhibits functional GLP‐1R and suggest that GLP‐1R‐mediated ERK‐signalling in sciatic nerve of diabetic rodents may protect large motor fibre function and small C fibre structure by a mechanism independent of glycaemic control.
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GLP-1 can modulate peripheral nerves through ERK signaling pathway, reducing occurrence of neurological dysfunction.
“GLP-1 can modulate peripheral nerves through the ERK (extracellular signal-regulated kinase) signaling pathway, reducing the occurrence of neurological dysfunction.400”
From Glucagon-like peptide-1 receptor: mechanisms and advances in therapy (2024) · cites this paper as [400]
The Conclusions suggest that GLP-1R-mediated ERK signaling in the sciatic nerve of diabetic rodents may protect motor-fibre function and sensory-fibre structure. The Discussion reports ERK activation and protection against nerve dysfunction in diabetic mice, but does not establish that ERK signaling caused the protection or that GLP-1 reduces neurological dysfunction generally. (LLM, conf=0.86)
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- Authors
- Jolivalt, C. G., Fineman, M., Deacon, C. F., Carr, R. D., & Calcutt, N. A.
- Affiliations
- University of California San Diego (US)
- University of Copenhagen (DK)
- Novo Nordisk (Denmark) (DK)
- Corresponding author
- Jolivalt, C. G.
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2011-09-28
- Volume
- 13
- Issue
- 11
- Pages
- 990-1000
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- PMC
- PMC3177968
- OpenAlex
- W2021375788
- Cited by
- 87
- References
- 47
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 5 · 2017: 3 · 2016: 6 · 2015: 6 · 2014: 6 · 2013: 9 · 2012: 4
- FWCI
- 4.58
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Diabetes Obesity and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Novo Nordisk
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK057629)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Health Sciences › Medicine › Neurology › Peripheral Neuropathies and Disorders
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, ERK signaling, diabetic peripheral neuropathy, exenatide, sciatic nerve, dorsal root ganglia, Schwann cells, motor nerve conduction velocity, streptozotocin-induced diabetes, neuroprotection
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Diabetes Mellitus, Experimental, Diabetic Neuropathies, Hypoglycemic Agents, Neural Conduction, Sciatic Nerve, Signal Transduction, Receptors, Glucagon, MAP Kinase Signaling System, Mice, Rats, Glucagon-Like Peptide 1
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