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K Sotiropoulos; Protein Kinase C (PKC) Activation in Circulating Mononuclear Cells - Potential Surrogate Marker for Diabetic Retinopathy and Other Microangiopathic Diseases . Invest. Ophthalmol. Vis. Sci. 2002;43(13):557.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Activation of the protein kinase C b isoform (PKCb) by hyperglycemia may mediate diabetic retinopathy and nephropathy, although no data correlates PKC activation with vascular disease severity in diabetic patients. We measured PKC activity in mononuclear cells (MCs) and evaluated this activity in diabetic animals and patients with respect to glycemic control and severity of diabetic complications. Method: Rats (control, streptozotocin-induced diabetic, diabetic treated with insulin and diabetic treated with PKCb inhibitor) were sacrificed 2 wks after the onset of diabetes and MCs, heart, aorta, kidney and retina isolated. In addition, 72 patients with type 1 & 2 diabetes and 22 nondiabetic subjects were studied. PKC activity was evaluated in MCs by an in situ method and retinal fundus photographs were graded by ETDRS criteria. Results: PKC activity in MCs was increased in diabetic rats by 71% as compared to control rats and was correlated with increased PKC activity in the retina (r2=0.70, P<0.001), heart (r2=0.64, P<0.001) and aorta (r2=0.28, P<0.001). PKCb activation was normalized in MCs and all vascular tissues by treatment with either insulin or PKCb inhibitor. In diabetic patients, PKC activity in MCs was increased 60% (P<0.001) over control and was correlated with HbA1C (P<0.001), disease duration (P=0.01) and age (P=0.01). PKC activation was correlated with severity of retinopathy (P<0.001) being increased 25%, 40% and 100% as compared to controls in those with no retinopathy, nonproliferative and proliferative retinopathy, respectively. Similar correlations were found with severity of nephropathy. Multi-variant analysis showed PKC activation in MCs as a risk factor independent of HbA1C and age for the development of PDR. Conclusion: These data provide the first evidence to correlate PKC activation with diabetic retinopathy in patients, and suggest that PKC activation in mononuclear cells may serve as a surrogate marker for diabetic microangiopathy and therapeutic adequacy of PKCb inhibition.
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