ArticleThe Journal of biological chemistry2017
Apelin-36 Modulates Blood Glucose and Body Weight Independently of Canonical APJ Receptor Signaling.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Myokines and mitochondrial function in cardiometabolic diseases.Journal of physiology and biochemistry · 2026Review
- International Union of Basic and Clinical Pharmacology. CXXI. Apelin receptor pharmacology in the human cardiovascular system and emerging clinical applications.Pharmacological reviews · 2026Review
- Single-cell transcriptomic analyses reveal angiogenic vascular responses to chronic cerebral hypoperfusion.iScience · 2026Article
- Metabolically stable apelin analogs: development and functional role in water balance and cardiovascular function.Clinical science (London, England : 1979) · 2025Review
- Rare Variants of Obesity-Associated Genes in Young Adults with Abdominal Obesity.Journal of personalized medicine · 2023Article
- Functionally Significant Variants in Genes Associated with Abdominal Obesity: A Review.Journal of personalized medicine · 2023Review
- Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update.Clinical medicine insights. Endocrinology and diabetes · 2022Review
- Breast milk apelin level increases with maternal obesity and high-fat feeding during lactation.International journal of obesity (2005) · 2021Article
- Apelin and Vasopressin: The Yin and Yang of Water Balance.Frontiers in endocrinology · 2021Review
- Article
- Remodeling adipose tissue inflammasome for type 2 diabetes mellitus treatment: Current perspective and translational strategies.Bioengineering & translational medicine · 2020Review
- Development and validation of an LC-MS/MS method for detection and quantification of in vivo derived metabolites of [PyrScientific reports · 2019Article
- Pioglitazone protects blood vessels through inhibition of the apelin signaling pathway by promoting KLF4 expression in rat models of T2DM.Bioscience reports · 2019Article
- Peptide hormone ELABELA enhances extravillous trophoblast differentiation, but placenta is not the major source of circulating ELABELA in pregnancy.Scientific reports · 2019Article
- Article
- International Union of Basic and Clinical Pharmacology. CVII. Structure and Pharmacology of the Apelin Receptor with a Recommendation that Elabela/Toddler Is a Second Endogenous Peptide Ligand.Pharmacological reviews · 2019Review
- Catalpol in Diabetes and its Complications: A Review of Pharmacology, Pharmacokinetics, and Safety.Molecules (Basel, Switzerland) · 2019Review
- Proapelin is processed extracellularly in a cell line-dependent manner with clear modulation by proprotein convertases.Amino acids · 2019Article
- Apelinergic System Structure and Function.Comprehensive Physiology · 2017Review
- Bioactivity of the putative apelin proprotein expands the repertoire of apelin receptor ligands.Biochimica et biophysica acta. General subjects · 2017Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apelin-36 was discovered as the endogenous ligand for the previously orphan receptor APJ. Apelin-36 has been linked to two major types of biological activities: cardiovascular (stimulation of cardiac contractility and suppression of blood pressure) and metabolic (improving glucose homeostasis and lowering body weight). It has been assumed that both of these activities are modulated through APJ. Here, we demonstrate that the metabolic activity of apelin-36 can be separated from canonical APJ activation. We developed a series of apelin-36 variants in which evolutionarily conserved residues were mutated, and evaluated their ability to modulate glucose homeostasis and body weight in chronic mouse models. We found that apelin-36(L28A) retains full metabolic activity, but is 100-fold impaired in its ability to activate APJ. In contrast to its full metabolic activity, apelin-36(L28A) lost the ability to suppress blood pressure in spontaneously hypertensive rats (SHR). We took advantage of these findings to develop a longer-acting variant of apelin-36 that could modulate glucose homeostasis without impacting blood pressure (or activating APJ). Apelin-36-[L28C(30kDa-PEG)] is 10,000-fold less potent than apelin-36 at activating the APJ receptor but retains its ability to significantly lower blood glucose and improve glucose tolerance in diet-induced obese mice. Apelin-36-[L28C(30kDa-PEG)] provides a starting point for the development of diabetes therapeutics that are devoid of the blood pressure effects associated with canonical APJ activation.
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