科研之友
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摘要
Dysfunctional insulin signaling is a key component of type 2 diabetes. Little is understood of the effects of systemic diabetes on retinal insulin signaling. Anumber of agents are used to treat patients with type 2 diabetes to normalize glucose levels and improve insulin signaling; however, little has been done to investigate the effects of these agents on retinal insulin signal transduction. We hypothesized that pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist, would normalize retinal insulin signal transduction through reduced tumor necrosis factor alpha (TNF alpha) and suppressor of cytokine signaling 3 (SOCS3) activities in whole retina and retinal endothelial cells (REC) and Muller test this hypothesis, we used the BBZDR/Wor type 2 diabetic rat model, as well as REC and Muller cells cultured in normoglycemia and hyperglycemic conditions, to investigate the effects of pioglitazone on TNF alpha, SOCS3, and downstream insulin signal transduction proteins. We also evaluated pioglitazone's effects on retinal function using electroretinogram and markers of apoptosis. Data demonstrate that 2 months of pioglitazone significantly increased electroretinogram amplitudes in type 2 diabetic obese rats, which was associated with improved insulin receptor activation. These changes occurred in both REC and Muller cells treated with pioglitazone, suggesting that these two cell types are key to insulin resistance in the retina. Taken together, these data provide evidence of impaired insulin signaling in type 2 diabetes rats, which was improved by increasing PPAR gamma activity. Further investigations of PPAR gamma actions in the retina may provide improved treatment options.
- 出版日期2014-9-19
