دورية أكاديمية

Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

التفاصيل البيبلوغرافية
العنوان: Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps
المؤلفون: Qi, Yong, Longo, Kenneth A, Giuliana, Derek J, Gagne, Samantha, McDonagh, Tom, Govek, Elizabeth, Nolan, Anna, Zou, Chaoseng, Morgan, Kristen, Hixon, Jeffrey, Saunders, Jeffrey O, DiStefano, Peter S, Geddes, Brad J
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2011
المجموعة: BioMed Central
الوصف: Background We and others have demonstrated previously that ghrelin receptor ( GhrR ) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1 st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both ...
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: http://www.biomedcentral.com/1472-6793/11/1Test
الإتاحة: http://www.biomedcentral.com/1472-6793/11/1Test
حقوق: Copyright 2011 Qi et al; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.82D1AC10
قاعدة البيانات: BASE