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

摘要: Background: We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) increased insulin sensitivity metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is dramatic decrease in hepatic steatosis. To characterize further underlying mechanisms glucose homeostasis mice, we conducted both hyperglycemic (HG) hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, investigated tissue uptake specifically examined liver sensitivity. Results: Consistent with tolerance-test data, HG clamp experiments, showed reduction glucose-stimulated release Nevertheless, robust 1 st phase secretion was still achieved, indicating healthy b-cell response maintained. significantly infusion rate reduced requirement for maintenance clamp, consistent their In HI-E clamps, LFD-fed higher peripheral littermates as indicated by significant increase insulin-stimulated disposal (Rd), decreased production (HGP). marked variety tissues, including skeletal muscle, brown adipose white tissue. HFD also modest, but conversion pyruvate glucose, would be anticipated if these displayed levels UCP2 UCP1 were BAT, respectively, mice. Conclusions: These results indicate improved characterized improvements normal metabolically challenged states, controls. an intact require less disposal. Our experiments reveal due BW independent dependent factors. provide several lines evidence key during challenge.