Oxidant-NO-dependent gene regulation in dogs with type I diabetes

The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n=4). The array data revealed that 797 genes were differentially expressed (P<0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. Mongrel dogs (weighing 22-29 kg, n = 13) were chronically instrumented for measurements of systemic hemodynamics. The control hemodynamics were recorded 10-14 days after the surgery. After the control recording, the dogs were divided into two groups: one normal (n = 7) and the other diabetic (n = 6). In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. Alloxan was prepared as a 5% solution in citrate buffer (pH 4-4.5). Only dogs with blood glucose >200 mg/dl (fasted for at least 16 h) on day 7 were included in the diabetic group. Before and after the development of diabetes, the dogs had free access to water. Systemic hemodynamics were measured again after 4-5 wk. All the microarray analysis were perormed after 4 weeks of alloxan injection.