Almon Richard R, DuBois Debra C, Lai William, Xue Bai, Nie Jing, Jusko William J
Department of Biological Sciences, State University of New York at Buffalo, Buffalo, New York 14260, USA.
J Endocrinol. 2009 Mar;200(3):331-46. doi: 10.1677/JOE-08-0404. Epub 2008 Dec 12.
Progression of diabetes was studied in male Goto-Kakizaki (GK) spontaneously diabetic rats between 4 and 20 weeks of age, and compared with Wistar-Kyoto (WKY) controls. Five animals from each strain were killed at 4, 8, 12, 16, and 20 weeks of age. Body weight, plasma glucose, and plasma insulin were measured. WKY rats showed a significantly larger weight gain than GK animals from 8 weeks of age onward. Plasma glucose was relatively stable in WKY. By contrast, plasma glucose was higher in GK than WKY even at 4 weeks and continued to increase up to 12 weeks and then maintained a hyperglycemic plateau throughout the remainder of the experiment. Plasma insulin was relatively stable in WKY from 8 weeks onward but was sharply elevated in GK between 4 and 8 weeks. After 8 weeks, insulin declined in GK with GK concentrations lower than WKY at 20 weeks, suggesting beta-cell failure. Gene expression in liver was explored using Affymetrix 230-2 gene arrays. Data mining identified 395 probe sets out of more than 31,000 that were differentially regulated. Excluding unidentifiable probe sets and considering duplicate probe sets, there were 311 genes that were expressed differently in the liver of the two strains. A functional analysis of these genes indicated that disruption of lipid metabolism in the liver is a major consequence of the chronic hyperglycemia in the GK strain. In addition, the results suggest that chronic inflammation contributes significantly to the development of diabetes in the GK rats.
研究了4至20周龄雄性Goto-Kakizaki（GK）自发性糖尿病大鼠的糖尿病进展情况，并与Wistar-Kyoto（WKY）对照大鼠进行比较。在4、8、12、16和20周龄时，从每个品系中处死5只动物。测量体重、血浆葡萄糖和血浆胰岛素。从8周龄起，WKY大鼠的体重增加明显大于GK动物。WKY大鼠的血浆葡萄糖相对稳定。相比之下，即使在4周龄时，GK大鼠的血浆葡萄糖也高于WKY大鼠，并且持续升高至12周，然后在实验的剩余时间内维持高血糖平台期。从8周龄起，WKY大鼠的血浆胰岛素相对稳定，但GK大鼠在4至8周期间胰岛素急剧升高。8周后，GK大鼠的胰岛素水平下降，在20周时GK大鼠的胰岛素浓度低于WKY大鼠，提示β细胞功能衰竭。使用Affymetrix 230-2基因芯片探索肝脏中的基因表达。数据挖掘在31000多个探针集中鉴定出395个差异调节的探针集。排除无法识别的探针集并考虑重复的探针集后，有311个基因在两个品系的肝脏中表达不同。对这些基因的功能分析表明，肝脏中脂质代谢的紊乱是GK品系慢性高血糖的主要后果。此外，结果表明慢性炎症对GK大鼠糖尿病的发展有显著贡献。
