Chavez Alberto O, Lopez-Alvarenga Juan C, Tejero M Elizabeth, Triplitt Curtis, Bastarrachea Raul A, Sriwijitkamol Apiradee, Tantiwong Puntip, Voruganti V Saroja, Musi Nicolas, Comuzzie Anthony G, DeFronzo Ralph A, Folli Franco
Diabetes Division, Department of Medicine, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr., San Antonio, TX 78229, USA.
Diabetes. 2008 Apr;57(4):899-908. doi: 10.2337/db07-0790. Epub 2008 Jan 3.
To quantitate insulin sensitivity in lean and obese nondiabetic baboons and examine the underlying cellular/molecular mechanisms responsible for impaired insulin action to characterize a baboon model of insulin resistance.
Twenty baboons received a hyperinsulinemic-euglycemic clamp with skeletal muscle and visceral adipose tissue biopsies at baseline and at 30 and 120 min after insulin. Genes and protein expression of key molecules involved in the insulin signaling cascade (insulin receptor, insulin receptor substrate-1, p85, phosphatidylinositol 3-kinase, Akt, and AS160) were sequenced, and insulin-mediated changes were analyzed.
Overall, baboons show a wide range of insulin sensitivity (6.2 +/- 4.8 mg x kg(-1) x min(-1)), and there is a strong inverse correlation between indexes of adiposity and insulin sensitivity (r = -0.946, P < 0.001 for % body fat; r = -0.72, P < 0.001 for waist circumference). The genes and protein sequences analyzed were found to have approximately 98% identity to those of man. Insulin-mediated changes in key signaling molecules were impaired both in muscle and adipose tissue in obese insulin-resistant compared with lean insulin-sensitive baboons.
The obese baboon is a pertinent nonhuman primate model to examine the underlying cellular/molecular mechanisms responsible for insulin resistance and eventual development of type 2 diabetes.
定量分析瘦型和肥胖型非糖尿病狒狒的胰岛素敏感性，并研究胰岛素作用受损的潜在细胞/分子机制，以表征胰岛素抵抗的狒狒模型。
20只狒狒接受了高胰岛素-正常血糖钳夹试验，在基线、胰岛素注射后30分钟和120分钟时采集骨骼肌和内脏脂肪组织活检样本。对胰岛素信号级联反应中关键分子（胰岛素受体、胰岛素受体底物-1、p85、磷脂酰肌醇3激酶、Akt和AS160）的基因和蛋白表达进行测序，并分析胰岛素介导的变化。
总体而言，狒狒表现出广泛的胰岛素敏感性（6.2±4.8 mg·kg⁻¹·min⁻¹），肥胖指标与胰岛素敏感性之间存在强烈的负相关（体脂百分比：r = -0.946，P < 0.001；腰围：r = -0.72，P < 0.001）。所分析的基因和蛋白序列与人类的序列具有约98%的同源性。与瘦型胰岛素敏感的狒狒相比，肥胖胰岛素抵抗的狒狒肌肉和脂肪组织中胰岛素介导的关键信号分子变化均受损。
肥胖狒狒是一种合适的非人类灵长类动物模型，可用于研究胰岛素抵抗及2型糖尿病最终发展的潜在细胞/分子机制。
