Hayden Melvin R, Karuparthi Poorna R, Manrique Camila Margarita, Lastra Guido, Habibi Javad, Sowers James R
Department of Internal Medicine, University of Missouri School of Medicine, Columbia, MO 65212, USA.
Exp Biol Med (Maywood). 2007 Jun;232(6):772-9.
In 2004, the human islet amyloid polypeptide (HIP) rat model was created by transfecting the Sprague-Dawley rat with the human islet amyloid polypeptide (hIAPP)-amylin gene. The objective of this study is to utilize the transmission electron microscope to study the longitudinal cellular and extracellular morphological changes within the islets of this model at 4, 8, and 14 months of age. It has been previously demonstrated that the 2-, 5-, and 10-month HIP models have no diabetes, impaired fasting glucose, and diabetes, respectively. The 4-month HIP model (FBS 123 mg/dl) demonstrated an abundance of beta-cells and insulin secretory granules with significant pericapillary and inter-beta-cell islet amyloid deposition. The 8-month model (FBS 187 mg/dl) demonstrated extensive islet amyloid deposition and marked changes of beta-cell apoptosis. The 14-month-old model (FBS 244 mg/dl) demonstrated islet and beta-cell atrophy with even greater amounts of extracellular islet amyloid compared to the 4-month-old and 8-month-old models. Functional beta cells were sparse and were associated with intra islet adipose deposition. These findings of ultrastructure cellular and extracellular morphological longitudinal remodeling changes in this novel animal model of type 2 diabetes may provide investigators with a better understanding regarding the role of islet amyloid in human islet.
2004年，通过将人胰岛淀粉样多肽（hIAPP）-胰淀素基因转染到斯普拉格-道利大鼠体内，创建了人胰岛淀粉样多肽（HIP）大鼠模型。本研究的目的是利用透射电子显微镜研究该模型在4个月、8个月和14个月龄时胰岛内细胞和细胞外形态的纵向变化。此前已证明，2个月、5个月和10个月的HIP模型分别没有糖尿病、空腹血糖受损和糖尿病。4个月的HIP模型（空腹血糖123mg/dl）显示β细胞和胰岛素分泌颗粒丰富，毛细血管周围和β细胞间有大量胰岛淀粉样沉积。8个月的模型（空腹血糖187mg/dl）显示广泛的胰岛淀粉样沉积和β细胞凋亡的明显变化。14个月大的模型（空腹血糖244mg/dl）显示胰岛和β细胞萎缩，与4个月和8个月大的模型相比，细胞外胰岛淀粉样物质含量更高。功能性β细胞稀少，且与胰岛内脂肪沉积有关。在这个新的2型糖尿病动物模型中，超微结构细胞和细胞外形态纵向重塑变化的这些发现，可能会让研究人员更好地了解胰岛淀粉样蛋白在人类胰岛中的作用。
