Servicio de Cardiología, Hospital de San Pedro, Logroño, Calle Piqueras, 98 26006 Logroño, La Rioja, Spain.
Diabetol Metab Syndr. 2014 Jan 27;6(1):10. doi: 10.1186/1758-5996-6-10.
The obese Zücker diabetic fatty male rat (ZDF:Gmi™-fa) is an animal model of type II diabetes associated with obesity and related metabolic disturbances like dyslipidaemia and diabetic nephropathy. In addition, diabetic dyslipidaemia has been linked to vascular and glomerular damage too. Dietary fat restriction is a current strategy to tackle obesity and, telmisartan, as a renoprotective agent, may mediate cholesterol efflux by activating PPARγ. To test the hypothesis that both therapeutical alternatives may influence dyslipidaemia and nephropathy in the ZDF rat, we studied their effect on development of diabetes.
Male Zücker Diabetic Fatty (ZDF) rats received a low-calorie diet, vehicle or telmisartan for 9 weeks. Blood samples were obtained for analyses of lipids and lipoproteins, LDL-oxidisability, HDL structural and functional properties. Urinalysis was carried out to estimate albumin loss. At the end of the experimental period, rats were sacrificed, liver extracted and APOA1 mRNA quantified.
Results indicated that low-calorie diet and telmisartan can slower the onset of overt hyperglycaemia and renal damage assessed as albuminuria. Both interventions decreased the oxidative susceptibility of LDL and hepatic APOA1 mRNA expression but only dietary restriction lowered hyperlipidaemia.
Either a dietary or pharmacologic interventions with telmisartan have important beneficial effects in terms of LDL oxidative susceptibility and progression of albuminuria in obesity related type II diabetes.
肥胖型 Zücker 糖尿病肥胖雄性大鼠（ZDF：Gmi™-fa）是一种与肥胖相关的 2 型糖尿病动物模型，伴有脂代谢紊乱，如血脂异常和糖尿病肾病。此外，糖尿病性脂代谢紊乱也与血管和肾小球损伤有关。限制饮食中的脂肪摄入是目前解决肥胖问题的一种策略，而替米沙坦作为一种肾保护剂，通过激活 PPARγ，可能介导胆固醇外流。为了验证这一假说，即这两种治疗选择可能影响 ZDF 大鼠的脂代谢紊乱和肾病，我们研究了它们对糖尿病发展的影响。
雄性 Zücker 糖尿病肥胖（ZDF）大鼠接受低热量饮食、载体或替米沙坦治疗 9 周。采集血样进行脂质和脂蛋白分析、LDL 氧化易感性、HDL 结构和功能特性分析。进行尿分析以估计白蛋白丢失。在实验期末，处死大鼠，提取肝脏并定量 APOA1 mRNA。
结果表明，低热量饮食和替米沙坦均可减缓明显高血糖和肾功能损害（如白蛋白尿）的发生。两种干预措施均降低了 LDL 的氧化易感性和肝 APOA1 mRNA 表达，但只有饮食限制降低了高脂血症。
无论是饮食干预还是替米沙坦的药物干预，在肥胖相关 2 型糖尿病中，均对 LDL 氧化易感性和白蛋白尿进展具有重要的有益作用。
