Adaptation of b-cell and Endothelial Function to XXXX Loading: Influence of Insulin Resistance.

@entity2299 @entity384 @entity409 @entity1735 @entity413
UNASSIGNED: High- @entity1735 diets have been associated with   -cell strain, @entity2299 , and @entity409 . We examined how b-cell and endothelial function adapt to @entity1735 overloading and the influence of insulin resistance. On sequential days in randomized order, nondiabetic subjects (classified as insulin-sensitive (IS, n=64) or insulin-resistant (IR, n=79) by euglycemic clamp) received 4 mixed meals over 14 hours with either standard (300 kcal) or double @entity1735 content. b-cell function was reconstructed by mathematical modeling; brachial artery @entity384 ( @entity384 ) was measured before and after each meal. Compared with IS, IR subjects showed higher glycemias and insulin hypersecretion due to greater   -cell @entity413 and rate sensitivity; potentiation of insulin secretion, however, was impaired. Circulating FFA were less suppressed in IR than IS subjects. Baseline @entity384 was reduced in IR, and postprandial @entity384 attenuation occurred after each meal, particularly with high @entity1735 , similarly in IR and IS. Throughout the 2 study days, higher FFA levels were significantly associated with lower (incretin-induced) potentiation and impaired @entity384 . In nondiabetic individuals, enhanced @entity413 sensitivity and potentiation upregulate the insulin secretory response to @entity1735 overloading. With insulin resistance this adaptation is impaired. Defective suppression of endogenous FFA is one common link between impaired potentiation and vascular @entity409 .
