title: Adaptation of β-Cell and Endothelial Function to Carbohydrate Loading: Influence of Insulin Resistance.
abstract: High-carbohydrate diets have been associated with β-cell strain, dyslipidemia, and endothelial dysfunction. We examined how β-cell and endothelial function adapt to carbohydrate 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 four mixed meals over 14 h with either standard (300 kcal) or double carbohydrate content. β-Cell function was reconstructed by mathematical modeling; brachial artery flow-mediated dilation (FMD) was measured before and after each meal. Compared with IS, IR subjects showed higher glycemia and insulin hypersecretion due to greater β-cell glucose and rate sensitivity; potentiation of insulin secretion, however, was impaired. Circulating free fatty acids (FFAs) were less suppressed in IR than IS subjects. Baseline FMD was reduced in IR, and postprandial FMD attenuation occurred after each meal, particularly with high carbohydrate, similarly in IR and IS. Throughout the two study days, higher FFA levels were significantly associated with lower (incretin-induced) potentiation and impaired FMD. In nondiabetic individuals, enhanced glucose sensitivity and potentiation upregulate the insulin secretory response to carbohydrate overloading. With insulin resistance, this adaptation is impaired. Defective suppression of endogenous FFA is one common link between impaired potentiation and vascular endothelial dysfunction.
authors.affiliation: Behavioral Medicine Research Center, University of Miami, Miami, FL Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, FL Department of Psychology, University of Miami, Coral Gables, FL.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Hurwitz
authors.affiliation: Behavioral Medicine Research Center, University of Miami, Miami, FL Department of Psychology, University of Miami, Coral Gables, FL.
authors.forename: Neil
authors.initials: N
authors.lastname: Schneiderman
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Marks
authors.affiliation: Behavioral Medicine Research Center, University of Miami, Miami, FL Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Armando J
authors.initials: AJ
authors.lastname: Mendez
authors.affiliation: Behavioral Medicine Research Center, University of Miami, Miami, FL.
authors.forename: Alex
authors.initials: A
authors.lastname: Gonzalez
authors.affiliation: Behavioral Medicine Research Center, University of Miami, Miami, FL Department of Psychology, University of Miami, Coral Gables, FL.
authors.forename: Maria M
authors.initials: MM
authors.lastname: Llabre
authors.affiliation: Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, FL.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Smith
authors.affiliation: National Research Council Institute of Biomedical Engineering, Padua, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bizzotto
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Santini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Manca
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism, Miller School of Medicine, University of Miami, Miami, FL.
authors.forename: Jay S
authors.initials: JS
authors.lastname: Skyler
authors.affiliation: National Research Council Institute of Biomedical Engineering, Padua, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mari
authors.affiliation: Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy National Research Council Institute of Clinical Physiology, Pisa, Italy ferranni@ifc.cnr.it.
authors.forename: Ele
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000222:Adaptation, Physiological; D000328:Adult; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D004730:Endothelium, Vascular / Q000502:physiology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008297:Male; D008962:Models, Theoretical; D014664:Vasodilation
chemical_list: D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified