title: NEFA-glucose comodulation model of beta-cell insulin secretion in 24-h multiple-meal test.
abstract: There is experimental evidence that a source of fatty acids (FAs) that is either exogenous or endogenous is necessary to support normal insulin secretion. Therefore, FAs comodulate the glucose-induced pancreatic insulin secretion. To assess the role of FAs, 16 morbidly obese nondiabetic patients and 6 healthy volunteers were studied. The controls and the obese subjects, before and after diet-induced weight loss, spent 24 h in a calorimetric chamber, where they consumed standardized meals. Hourly blood samples were drawn from a central venous catheter for the measurement of glucose, C-peptide, and nonesterified fatty acid (NEFA) concentrations. Insulin sensitivity was measured (as the M value) by euglycemic hyperinsulinemic clamp. In the present study, we propose a mathematical model in which insulin secretion rate (ISR) is expressed as a function of both plasma glucose and NEFA concentrations. Model parameters, obtained by fitting the individual experimental data of plasma C-peptide concentration, gave an estimated ISR comparable with that obtained by the deconvolution method. To evaluate the performance of the model in an experimental condition in which incretin effect was minimized, previous data on insulin secretion following a butter load and subsequent hyperglycemic clamp were reanalyzed. This model of nutrient-stimulated insulin secretion is the first attempt to represent in a simple way the interaction between glucose and NEFA in the regulation of insulin secretion in the beta-cell and explains, at least in part, the "potentiation factor" used in previous models to account for other control factors different from glucose after either an intravenous infusion of glucose or a mixed meal.
authors.affiliation: Department of Systems Analysis and Informatics, University of Rome La Sapienza, Italy. salinari@dis.uniroma1.it
authors.forename: Serenella
authors.initials: S
authors.lastname: Salinari
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bertuzzi
authors.forename: Melania
authors.initials: M
authors.lastname: Manco
authors.forename: Geltrude
authors.initials: G
authors.lastname: Mingrone
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D002096:C-Peptide / Q000097:blood; D002940:Circadian Rhythm; D004435:Eating; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008954:Models, Biological; D009767:Obesity, Morbid / Q000178:diet therapy / Q000503:physiopathology*; D009994:Osmolar Concentration; D015431:Weight Loss
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D005230:Fatty Acids, Nonesterified; D007328:Insulin