التفاصيل البيبلوغرافية
العنوان:
Susceptibility to fatty acid-induced β-cell dysfunction is enhanced in prediabetic diabetes-prone biobreeding rats: A potential link between β-cell lipotoxicity and islet inflammation
المؤلفون:
Adria Giacca , Andrei I. Oprescu , Marc Y. Donath , Anthony E. Naassan , Gary F. Lewis , Husam Ghanim , Jan A. Ehses , Astrid Chamson-Reig , Khajag Koulajian , Edith Arany , Tracy Goh , Paresh Dandona , Frederick Yoon , Christine Tang
المصدر:
Paediatrics Publications
بيانات النشر:
Scholarship@Western, 2013.
سنة النشر:
2013
مصطلحات موضوعية:
medicine.medical_specialty , medicine.medical_treatment , Type 2 diabetes , Real-Time Polymerase Chain Reaction , Pediatrics , Prediabetic State , Islets of Langerhans , Endocrinology , Insulin-Secreting Cells , Internal medicine , medicine , Animals , Rats, Inbred BB , Prediabetes , Chemokine CCL2 , Phospholipids , Type 1 diabetes , geography , geography.geographical_feature_category , business.industry , Insulin , Fatty Acids , medicine.disease , Islet , Immunohistochemistry , Interleukin-10 , Rats , Soybean Oil , Lipotoxicity , Emulsions , Female , business , Hyperglycemic agent , Biobreeding rat
الوصف:
β-Cell lipotoxicity is thought to play an important role in the development of type 2 diabetes. However, no study has examined its role in type 1 diabetes, which could be clinically relevant for slow-onset type 1 diabetes. Reports of enhanced cytokine toxicity in fat-laden islets are consistent with the hypothesis that lipid and cytokine toxicity maybe synergistic. Thus, β-cell lipotoxicity could be enhanced in models of autoimmune diabetes. To determine this, we examined the effects of prolonged free fatty acids elevation on β-cell secretory function in the prediabetic diabetes-prone BioBreeding (dp-BB) rat, its diabetes-resistant BioBreeding (dr-BB) control, and normal Wistar-Furth (WF) rats. Rats received a 48-h iv infusion of saline or Intralipid plus heparin (IH) (to elevate free fatty acid levels ∼2-fold) followed by hyperglycemic clamp or islet secretion studies ex vivo. IH significantly decreased β-cell function, assessed both by the disposition index (insulin secretion corrected for IH-induced insulin resistance) and in isolated islets, in dp-BB, but not in dr-BB or WF, rats, and the effect of IH was inhibited by the antioxidant N-acetylcysteine. Furthermore, IH significantly increased islet cytokine mRNA and plasma cytokine levels (monocyte chemoattractant protein-1 and IL-10) in dp-BB, but not in dr-BB or WF, rats. All dp-BB rats had mononuclear infiltration of islets, which was absent in dr-BB and WF rats. In conclusion, the presence of insulitis was permissive for IH-induced β-cell dysfunction in the BB rat, which suggests a link between β-cell lipotoxicity and islet inflammation. Copyright © 2013 by The Endocrine Society.
وصف الملف:
application/pdf
URL الوصول:
https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3b703d83d4bbb45a4a3e2633cc20ed1 https://ir.lib.uwo.ca/context/paedpub/article/1683/viewcontent/endo0089.pdf
حقوق:
OPEN
رقم الأكسشن:
edsair.doi.dedup.....e3b703d83d4bbb45a4a3e2633cc20ed1
قاعدة البيانات:
OpenAIRE
