Adiponectin: A Promising Target for the Treatment of Diabetes and Its Complications

Abstract

Diabetes mellitus, a chronic metabolic disorder characterized by hyperglycemia, presents a formidable global health challenge with its associated complications. Adiponectin, an adipocyte-derived hormone, has emerged as a significant player in glucose metabolism and insulin sensitivity. Beyond its metabolic effects, adiponectin exerts anti-inflammatory, anti-oxidative, and vasoprotective properties, making it an appealing therapeutic target for mitigating diabetic complications. The molecular mechanisms by which adiponectin impacts critical pathways implicated in diabetic nephropathy, retinopathy, neuropathy, and cardiovascular problems are thoroughly examined in this study. In addition, we explore possible treatment options for increasing adiponectin levels or improving its downstream signaling. The multifaceted protective roles of adiponectin in diabetic complications suggest its potential as a novel therapeutic avenue. However, further translational studies and clinical trials are warranted to fully harness the therapeutic potential of adiponectin in the management of diabetic complications. This review highlights adiponectin as a promising target for the treatment of diverse diabetic complications and encourages continued research in this pivotal area of diabetes therapeutics.

Keywords: AdipoRs; adiponectin; diabetes; pancreatic islets; single-cell RNAseq.

Figure 1

A presentation demonstrating the diverse pathways through which adiponectin receptors exert their functions. Adiponectin engages with its receptors to initiate various signaling pathways. AdipoR1 enhances calcium influx, leading to the activation of Ca²⁺/calmodulin-dependent protein kinase kinase β (CaMKKβ) and subsequent downstream kinases. AdipoR1- and R2-dependent signaling are mediated by adaptor protein phosphotyrosine interaction (APPL) 1, which allows LKB1 to translocate from the nucleus to the cytoplasm and activate AMPK, ceramidase activity, and peroxisome proliferator-activated receptor-alpha (PPAR-α). Activation of AMPK reduces gluconeogenesis, oxidative stress, and inflammation. On the other hand, activation of PPAR-α reduces lipotoxicity and inflammation and increases fatty acid oxidation. All these effects ultimately improve glycemic status.

Figure 2

Summary of tissue-specific functions of adiponectin. Mechanism of adiponectin actions in prevention of insulin resistance and diabetes.

Figure 3

A presentation illustrating the mechanism through which adiponectin functions as an antidiabetic agent.

Figure 4

Diagram depicting the investigated pathways illustrating the impacts of adiponectin on pancreatic β-cells.

Figure 5

Single-cell UMAP visualization depicting the cellular landscape comparison of Early db/db vs. Control (A) and Late db/db vs. Early db/db (B) of pancreatic islet cells. The differential expression of critical genes in adiponectin signaling, apoptosis, β-cell function, oxidative stress, inflammation, and cellular growth are depicted in color indications (C).