Potential Therapeutic Role for Apelin and Related Peptides in Diabetes: An Update

Abstract

Type 2 diabetes mellitus (T2DM) is an epidemic with an ever-increasing global prevalence. Current treatment strategies, although plentiful and somewhat effective, often fail to achieve desired glycaemic goals in many people, leading ultimately to disease complications. The lack of sustained efficacy of clinically-approved drugs has led to a heightened interest in the development of novel alternative efficacious antidiabetic therapies. One potential option in this regard is the peptide apelin, an adipokine that acts as an endogenous ligand of the APJ receptor. Apelin exists in various molecular isoforms and was initially studied for its cardiovascular benefits, however recent research suggests that it also plays a key role in glycaemic control. As such, apelin peptides have been shown to improve insulin sensitivity, glucose tolerance and lower circulating blood glucose. Nevertheless, native apelin has a short biological half-life that limits its therapeutic potential. More recently, analogues of apelin, particularly apelin-13, have been developed that possess a significantly extended biological half-life. These analogues may represent a promising target for future development of therapies for metabolic disease including diabetes and obesity.

Proteomic Analysis of Skeletal Muscle and White Adipose Tissue after Aerobic Exercise Training in High Fat Diet Induced Obese Mice

“…As an adipocytokine secreted by and sensed by adipocytes, apelin is necessary for the maintenance of insulin sensitivity and tends to counteract diabetes mellitus [ 6 ]. The apelin adipocyte signaling pathway can dampen ROS generation, increase mitochondrial biogenesis, and promote the browning of WAT [ 33 ]. Furthermore, our study observed several differentially regulated EFP proteins in the AE group that can mitigate diet-induced obesity, such as the upregulated PRDX5 [ 34 ] as well as the downregulated LAMA4 [ 35 ], S27A1 [ 36 ], and HS12A [ 37 ], as reported in previous studies.…”

Investigation of the Possible Relation of Apelin, Kynurenine and IL-4/IL-10/IL-12/Tnf-alfa Levels with Clinical and Metabolic Parameters in Obesity

“…A significant number of clinical studies investigating apelin levels in body fluids, both in healthy controls and in patients with different pathologies, have been reported. Recent research shows that apelin peptide may be a useful adipokine in metabolic disorders and be used as a promising therapeutic target for obesity and antidiabetic drugs [4,5]. Apelin is upregulated in obesity.…”

“…Many studies have reported that increased plasma apelin is associated with metabolic pathologies. Recent studies show that apelin peptide may be a useful adipokine in metabolic disorders and it can be a potential therapeutic target for obesity and antidiabetic drugs [4,5]. Apelin is upregulated in obesity.…”

The Effect of SGLT2 Inhibitor Dapagliflozin on Serum Levels of Apelin in T2DM Patients with Heart Failure

“…Numerous animal and clinical studies suggest that reduced levels of circulating apelin could be risk factor for HF, while an expression of its receptor was found to have been decreased in hypertrophic myocardium as well as in non-ischemic and ischemic tissues of kidneys [ 21 , 22 ]. Overall, the levels of apelin may be a promising indicator of cardiac remodeling and biomarker of effective management of HF [ 23 ]. Moreover, T2DM apelin peptides attenuated insulin resistance, improved glucose tolerance and reduced circulating fasting glucose [ 24 ].…”