Impaired β-Cell Function and Deposition of Fat Droplets in the Pancreas as a Consequence of Hypertriglyceridemia in OLETF Rat, a Model of Spontaneous NIDDM
Impaired β-Cell Function and Deposition of Fat Droplets in the Pancreas as a Consequence of Hypertriglyceridemia in OLETF Rat, a Model of Spontaneous NIDDM
复制标题
自发性 NIDDM 模型 OLETF 大鼠高甘油三酯血症导致 β 细胞功能受损和胰腺脂肪滴沉积
作者：
Z. Man;Min Zhu;Y. Noma;K. Toide;Takashi Sato;Yoshihiko Asahi;T. Hirashima;S. Mori;K. Kawano;A. Mizuno;T. Sano;K. Shima
高脂血症是肥胖相关的NIDDM的一个特征，但这种关联的病理学意义尚不清楚。采用体内和体外实验方法，观察了甘油三酯（TG）对6、12和30周龄雄性OLETF大鼠胰腺β细胞功能和形态学的影响，并以糖尿病抗性LETO大鼠作为正常对照。结果显示，在禁食状态下，与年龄匹配的LETO大鼠相比，OLETF大鼠的血浆TG在6周龄时增加了2.5倍，在12周龄时增加了3.3倍，在30周龄时增加了6.2倍。12周龄OLETF大鼠胰岛中TG含量显著高于同龄对照组，而6周龄OLETF大鼠胰岛中TG含量则无显著性差异。因此，将6周龄大鼠的胰岛与游离脂肪酸（FFA; 1.0 mmol/l油酸钠）或TG（5.0 mmoM Intralipide）一起培养72 h。与对照LETO大鼠的结果相反，OLETF大鼠中的几个异常是明显的：1）在27.7mmol/l葡萄糖存在下，葡萄糖诱导的胰岛素分泌被FFA或TG更多地抑制，这一结果至少部分地与胰岛中葡萄糖激酶活性降低有关; 2）在胰岛中发现TG含量显著升高; 30周龄时，油红O-胰岛素双染显示胰岛内有脂肪滴沉积，胰岛β细胞内也有脂肪滴沉积。总之，高甘油三酯血症导致胰岛中显著的TG储存，其随后至少部分地通过胰岛中葡萄糖激酶活性降低来抑制葡萄糖诱导的胰岛素分泌。因此，胰岛中的脂肪滴可能在加速该大鼠模型中NIDDM的发展中起重要作用。
Hypertriglyceridemia is known to be a feature of obesity-related NIDDM, but the patho-etiological significance of this association is obscure. The effects of triglycerides (TGs) on β-cell function and morphological changes in pancreas were examined using in vivo and in vitro approaches in male OLETF rats at ages 6, 12, and 30 weeks, with their diabetes-resistant counterpart, LETO rats, as normal controls. The results showed that, in the fasting state, plasma TGs in OLETF rats were increased 2.5-fold at age 6 weeks, 3.3-fold at age 12 weeks, and 6.2-fold at age 30 weeks, compared with age-matched LETO rats. The TG content in islets from 12-week-old OLETF rats was significantly increased when compared with those from their age-matched counterparts, but this was not the case with the 6-week-old OLETF rats. Therefore, the islets from 6-week-old rats were cultured with either free fatty acids (FFAs; 1.0 mmol/1 sodium oleate) or TG (5.0 mmoM Intralipide) for 72 h. Several abnormalities in OLETF rats were evident, in contrast to the results from control LETO rats: 1) glucose-induced insulin secretion was more inhibited by either FFAs or TGs in the presence of 27.7 mmol/l glucose, a result associated, at least in part, with reduced glucokinase activity in the islets; 2) a marked elevation in TG content was found in the islets; and 3) the deposition of fat droplets in the enlarged islets, even in the β-cells, was found by Oil Red O-insulin double staining at age 30 weeks. In conclusion, hypertriglyceridemia resulted in significant TG stores in the islets, which subsequently inhibited glucose-induced insulin secretion, at least in part, via reduced glucokinase activity in the islets. Fat droplets in islets, therefore, may play an important role in hastening the development of NIDDM in this rat model.
通过三个独立测定测量肝脏的葡萄糖磷酸化能力。
DOI：
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发表时间：
1986
期刊：
The Journal of biological chemistry
影响因子：
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作者：
Kuwajima,M;Newgard,CB;Foster,DW;McGarry,JD
通讯作者：
McGarry,JD
DOI：
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发表时间：
1994-08
期刊：
The Journal of biological chemistry
影响因子：
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作者：
J. Hamilton;V. Civelek;F. Kamp;K. Tornheim;B. Corkey
通讯作者：
J. Hamilton;V. Civelek;F. Kamp;K. Tornheim;B. Corkey
一种用于研究朗格汉斯岛胰岛素释放机制和钙代谢的亚细胞分级方法。
影响因子：
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作者：
McDaniel,ML;Colca,JR;Kotagal,N;Lacy,PE
通讯作者：
Lacy,PE