Objective: Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice. Methods: A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions. Results: Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment. Conclusion AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice.

● AIM: To investigate the role of advanced glycation endproducts (AGEs) in the pathogenesis of age-related macular degeneration (AMD).● METHODS: Bovine choroidal endothelial cells (CEC:)were isolated by the modified protocol using lycopersicon esculentum agglutinin coated Dynabeads, and identiffed by immunocytochemical staining with anti-Factor Ⅷ antibody and uptaking of dil-acetylated low-density lipoprotein (dil-ac-LDL). AGEs were prepared by incubating 50g/L bovine serum albumin and 150g/L glucose at 37℃ for 6wk, which were characterized by dot blot assay with anti-AGEs antibody. CEC proliferation was evaluated using 3,(4,5-dimethylthiazol-2-yl)-2,5- diphenyl tetrazolium bromide (MTT) assay, and tube formation in CEC was determined by a Vitrogen system.● RESULTS: More than 90% of the cultured cells were positive to Factor V immunostaining and had the ability to uptake dil-ac-LDL, which were the features of endothelial cells. AGEs we prepared were affinitive to anti-AGEs antibody. After treatment with AGEs for a time course of 3d, CEC proliferation was significantly increased in a dose-dependent manner by AGEs at concentrations between 62.5 and 500mg/L. The cytokine,basic fibroblast growth factor (bFGF), enhanced strongly tube-like structure formation in CEC to 124% (P＜0.05)above that of untreated controls. In this condition, AGEs at the concentrations of 500 and 50mg/L showed no effect on CEC tube formation (P＞0.05).● CONCLUSION: The present study demonstrated that CEC proliferation was increased by AGEs, however, regarding there was no statistically effect on CEC tube formation. These findings confirm and extend that AGEs could be a potential initiator in the pathogenesis of choroidal neovascularization in exudative AMD, at least in part, through enhancement of CEC proliferation.