Adiponectin accumulation in the retinal vascular endothelium and its possible role in preventing early diabetic microvascular damage

Abstract

Adiponectin (APN), a protein abundantly secreted from adipocytes, has been reported to possess beneficial effects on cardiovascular diseases in association with its accumulation on target organs and cells by binding to T-cadherin. However, little is known about the role of APN in the development of diabetic microvascular complications, such as diabetic retinopathy (DR). Here we investigated the impact of APN on the progression of early retinal vascular damage using a streptozotocin (STZ)-induced diabetic mouse model. Our immunofluorescence results clearly showed T-cadherin-dependent localization of APN in the vascular endothelium of retinal arterioles, which was progressively decreased during the course of diabetes. Such reduction of retinal APN accompanied the early features of DR, represented by increased vascular permeability, and was prevented by glucose-lowering therapy with dapagliflozin, a selective sodium-glucose co-transporter 2 inhibitor. In addition, APN deficiency resulted in severe vascular permeability under relatively short-term hyperglycemia, together with a significant increase in vascular cellular adhesion molecule-1 (VCAM-1) and a reduction in claudin-5 in the retinal endothelium. The present study demonstrated a possible protective role of APN against the development of DR.

Will GLP-1 Analogues and SGLT-2 Inhibitors Become New Game Changers for Diabetic Retinopathy?

“…Low retinal adiponectin concentrations that cause increased vascular permeability and have already been suggested to correlate with the development and progression of DR [ 68 ] were found to be prevented by dapagliflozin treatment [ 69 ]. SGLT-2 inhibitor-dependent low-grade hyperketonemia, resulting in shift of fuel metabolism from glucose and fat oxidation to more energy efficient and less oxidative stress producing ketone metabolism, has been suggested to account for the cardiorenal beneficial effects [ 70 ].…”

Adiponectin Paradox More Evident in Non-Obese Than in Obese Patients with Diabetic Microvascular Complications

“… 38 In addition, T-cadherin-dependent localization of adiponectin was identified in the retinal vascular endothelium of diabetic mice, suggesting it to play a role in preventing the development of diabetic retinopathy. 39 Similarly, increased albuminuria in adiponectin deficient mice was reduced by adiponectin administration. 40 In podocytes, adiponectin enhanced AMP-activated protein kinase (AMPK) through binding to AdipoR1, resulting in reduced oxidative stress and inflammation in the kidneys.…”

The Relationship between Serum Adiponectin, Urinary Albumin/Creatinine Ratio and Type 2 Diabetes: A Population-Based Cross-Sectional Study

“…Furthermore, since adiponectin has also been shown to be protective against diabetic complications, such as retinopathy and nephropathy in various mouse models [ 36 , 37 ], it would be interesting to evaluate the association between serum adiponectin concentration and diabetic complications in diabetic patients. The use of uACR-adjusted serum adiponectin concentrations, rather than serum adiponectin concentrations themselves, may allow for an accurate assessment of such associations.…”