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Preventive Effects Of Pioglitazone And Its Mechanism In NOD Mice

Posted on:2004-11-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H PeiFull Text:PDF
GTID:1104360092987038Subject:Internal Medicine
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Part I. The Effect of Pioglitazone on Incidence and Insulitis in NOD MiceObjective To explore the effects in prevention of insulitis and diabetes by pioglitazone in female NOD mice.Methods Female NOD mice at 4 weeks of age were divided into 3 groups and fed a regular diet (control group, n=25) and 0.01% (low dose group, n=23)or 0.04%(high dose group, n=25)pioglitazone food admixture from 4 to 30 weeks of age. Urine glucose in Mice checked weekly from 10 to 30 weeks of age, if positive, blood glucose were measured and diagnosed as diabetes if two consecutive blood glucose levels were 16.9mmol/l. Pancreas were removed from non-diabetic mice at 12 weeks of age to score insulitis severity by routine H-E staining .Resultsl.At 30 weeks of age, the incidence of diabetes was 80%(20/25) in the control group and 60.9%(14/23) in the low dose group, and 60%(15/25)in the high dose group.The initial diabetes onset was delayed about 2 weeks in pioglitazone groups compared to the control group (151.7 ?4.7 and 152.9 ?2.7 vs 139.2 ?8.2 days), but no statistical difference was found among these groups.2.At some time point, diabetes incidence of treated group showed lower than control group(p<0.05).Low dose treated group vs control group :( i )at 100 days of age, 0%(0/23) vs 16%(4/25);( ii )at 185 days of age, 39%(9/23)vs 68%(17/25).High dose group vs control group: ( i) at 110 days of age, 0%(0 /25)vs 16%(4/25); (ii) at 120 day of age, 4%(1 /25)vs24%(6/25); (iii) at 135 days of age, 12%(3/25)vs 36%(9/25).3.There was no difference in insulitis scores between control group (n=5)and low dose (n=4) or high dose (n=7) groups at 12 weeks of age (1.99 0.75 vs 1.01 0.68 and 1.19?.84, p=0.079 and p=0.118), But were significantly lower in the combined pioglitazone group (n=11)compared to control group up (1.12 0.75 vs 1.99 0.75, p=0.049).Conclusion Pioglitazone, to some extent, lessens insulitis severity and delays diabetes onset in female NOD mice, indicating its anti-inflammatory effects.
Keywords/Search Tags:NOD, pioglitazone, type 1 diabetes, insulitis
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