ArticleFEBS open bio2014
The di-peptide Trp-His activates AMP-activated protein kinase and enhances glucose uptake independently of insulin in L6 myotubes.
Article in FEBS open bio, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 36 citations in OpenAlex.
- Peptide Drug: Design and Clinical Applications.MedComm · 2025Review
- Oligopeptide/Histidine Transporter PHT1 and PHT2 - Function, Regulation, and Pathophysiological Implications Specifically in Immunoregulation.Pharmaceutical research · 2023Review
- A comprehensive review on the glucoregulatory properties of food-derived bioactive peptides.Food chemistry: X · 2022Article
- In vitro and in silico characterization of adiponectin-receptor agonist dipeptides.NPJ science of food · 2021Article
- Metformin suppresses breast cancer growth via inhibition of cyclooxygenase-2.Oncology letters · 2021Article
- Article
- Leucine-glycine and carnosine dipeptides prevent diabetes induced by multiple low-doses of streptozotocin in an experimental model of adult mice.Journal of diabetes investigation · 2019Article
- Effects of Glucose with Casein Peptide Supplementation on Post-Exercise Muscle Glycogen Resynthesis in C57BL/6J Mice.Nutrients · 2018Article
- Di- and tripeptide transport in vertebrates: the contribution of teleost fish models.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2017Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The di-peptide Trp-His (WH) has vasorelaxant and anti-atherosclerotic functions. We hypothesized that WH has multiple biological functions and may aid AMP-activated protein kinase (AMPK) activation and affect the glucose transport system in skeletal muscle. First, we examined whether WH or His-Trp (HW) can activate AMPKα. Treatment of L6 myotubes with WH or HW significantly increased phosphorylation of AMPKα. WH activated AMPK independently of insulin and significantly increased glucose uptake into L6 myotubes following translocation of glucose transporter 4 (Glut4) to the plasma membrane. This activation was induced by the LKB1 pathway but was independent of changes in intracellular Ca(2+) levels and the Ca(2+)/calmodulin-dependent kinase pathway. L6 myotubes express only one type of oligopeptide transporter, peptide/histidine transporter 1 (PHT1, also known as SLC15a4), and WH is incorporated into cells and activates AMPKα following PHT1-mediated cell uptake. These findings indicate that (1) WH activates AMPK and insulin independently enhances glucose uptake following translocation of Glut4 to the plasma membrane, (2) activation of AMPKα by WH is mediated by the LKB1 pathway, without altering the Ca(2+)-dependent pathway, and (3) L6 myotubes express only one type of peptide transporter (PHT1; SLC15a4), which incorporates WH into cells to activate AMPKα.
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