Badin Jill K, Progar Victor, Pareddy Anisha, Cagle Jordan, Alloosh Mouhamad, Sturek Michael
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana.
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana;, Email:
Comp Med. 2019 Apr 1;69(2):114-122. doi: 10.30802/AALAS-CM-18-000037. Epub 2019 Mar 20.
According to a single study in dogs that was conducted in 1949, the diabetic effects of the β-cell toxin alloxan are dependent on age. The current study examined whether this age-dependence of alloxan is present in the clinically relevant Ossabaw miniature swine () model of metabolic syndrome. Juvenile swine ( = 8; age, 4.3 ± 0.2 mo) and adult swine ( = 8; age, 7.4 ± 0.2 mo) received alloxan (average dosage, 140 mg/kg IV) and were placed on a hypercaloric, atherogenic diet for 6 mo. The metabolic syndrome profile was confirmed by measuring body weight, cholesterol, and triglycerides. Intravenous glucose tolerance testing was used to assess glucose clearance and peripheral plasma insulin levels. The β-cell mass was calculated by immunohistochemical staining of pancreatic tissue. Although juvenile and adult swine exhibited comparable severity of metabolic syndrome, adult swine developed impaired glucose clearance and elevated fasting blood glucose levels at 6 mo after alloxan administration on the atherogenic diet. Peripheral plasma insulin levels in juvenile and adult swine were comparable at all time points and lower than in nonalloxan-treated age-matched controls, which is reflected in the lower pancreatic β-cell mass of the 2 treated groups. However, compared with adult pigs, juvenile swine exhibited greater insulin response recovery (complete or partial restoration of peripheral insulin levels to reference values) at 6 mo after alloxan administration. Overall, these results indicate that youth can confer some protection against the diabetogenic effects of alloxan in swine, potentially due in part to the greater insulin response recovery of young pigs. This study supports previous research that the effects of alloxan are dependent on the developmental maturity of the animal.
根据1949年对犬类进行的一项单一研究，β细胞毒素四氧嘧啶的糖尿病效应取决于年龄。本研究调查了四氧嘧啶的这种年龄依赖性在代谢综合征临床相关的奥萨巴沃小型猪（）模型中是否存在。幼年猪（ = 8；年龄，4.3±0.2个月）和成年猪（ = 8；年龄，7.4±0.2个月）接受四氧嘧啶（平均剂量，140 mg/kg静脉注射），并接受高热量、致动脉粥样化饮食6个月。通过测量体重、胆固醇和甘油三酯来确认代谢综合征概况。静脉葡萄糖耐量试验用于评估葡萄糖清除率和外周血浆胰岛素水平。通过胰腺组织免疫组化染色计算β细胞量。尽管幼年和成年猪表现出相当程度的代谢综合征严重程度，但成年猪在接受致动脉粥样化饮食的四氧嘧啶给药6个月后出现葡萄糖清除受损和空腹血糖水平升高。幼年和成年猪的外周血浆胰岛素水平在所有时间点都相当，且低于未接受四氧嘧啶治疗的年龄匹配对照，这反映在两个治疗组较低的胰腺β细胞量上。然而，与成年猪相比，幼年猪在四氧嘧啶给药6个月后表现出更大的胰岛素反应恢复（外周胰岛素水平完全或部分恢复到参考值）。总体而言，这些结果表明，幼年可能对猪体内四氧嘧啶的致糖尿病作用具有一定的保护作用，这可能部分归因于幼猪更大的胰岛素反应恢复。本研究支持先前的研究，即四氧嘧啶的作用取决于动物的发育成熟度。
