التفاصيل البيبلوغرافية
| العنوان: |
Ubiquitination is involved in glucose-mediated downregulation of GIP receptors in islets. |
| المؤلفون: |
Jie Zhou, Livak, Mauren F. A., Bernier, Michel, Muller, Denis C., Carlson, Olga D., Elahi, Dariush, Maudsley, Stuart, Egan, Josephine M. |
| المصدر: |
American Journal of Physiology: Endocrinology & Metabolism; Aug2007, Vol. 293, pE538-E547, 10p, 8 Graphs |
| مصطلحات موضوعية: |
GASTROINTESTINAL hormones, GLUCOSE, PEOPLE with diabetes, DIABETES, UBIQUITIN, INSULIN, BLOOD sugar |
| مستخلص: |
Glucose-dependent insulinotropic polypeptide (GIP) is a gastrointestinal hormone that has a potent stimulatory effect on insulin release under conditions of normal glucose tolerance. However, its insulinotropic effect is reduced or even absent entirely in type 2 diabetic patients. In this study, we addressed the role of glucose concentration in the diabetic range of ≥11 mM, i.e., hyperglycemia per se, as a cause of the lack of response to GIP. Culturing rat and human pancreatic islets in ≥11 mM glucose for up to 24 h resulted in prevention of GIP-mediated intracellular cAMP increase compared with culturing in 5 mM glucose. Western blot analysis revealed a selective 67 ± 2% (rat) and 60 ± 8% (human) decrease of GIP-R expression in islets exposed to ≥11 mM glucose compared with 5 mM glucose (P < 0.001). We further immunoprecipitated GIP-R from islets and found that GIP-R was targeted for ubiquitination in a glucose- and time-dependent manner. Downregulation of GIP-R was rescued by treating isolated islets with proteasomal inhibitors lactacystin and MG-132, and the islets were once again capable of increasing intracellular cAMP levels in response to GIP. These results suggest that the GIP-R is ubiquitated, resulting in downregulation of the actions of GIP. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
