Impaired beta-cell function and deposition of fat droplets in the pancreas as a consequence of hypertriglyceridemia in OLETF rat, a model of spontaneous NIDDM
| Autor: | Toshiaki Sano, Yoshihiko Noma, Min Zhu, Shigehito Mori, Takashi Sato, Akira Mizuno, Zhi-Wei Man, Kazuya Kawano, Kenji Shima, Tsukasa Hirashima, Kiyotaka Toide, Yoshihiko Asahi |
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| Rok vydání: | 1997 |
| Předmět: |
Male
medicine.medical_specialty X Chromosome Endocrinology Diabetes and Metabolism medicine.medical_treatment Biology Fatty Acids Nonesterified Rats Mutant Strains chemistry.chemical_compound Islets of Langerhans In vivo Diabetes mellitus Internal medicine Glucokinase Insulin Secretion Internal Medicine medicine Animals Insulin Pancreas Cells Cultured Triglycerides Hypertriglyceridemia geography geography.geographical_feature_category Triglyceride Chromosome Mapping medicine.disease Islet Lipids Rats Endocrinology L-Glucose chemistry Diabetes Mellitus Type 2 |
| Zdroj: | Diabetes. 46(11) |
| ISSN: | 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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