title: Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia.
abstract: Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2-4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l⁻¹·min, P < 0.001), with left-shifted insulin secretion (AUC(0-15): MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion.
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Torsten P
authors.initials: TP
authors.lastname: Vahl
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Benedikt A
authors.initials: BA
authors.lastname: Aulinger
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Eric P
authors.initials: EP
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Drazen
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Yve
authors.initials: Y
authors.lastname: Ulrich-Lai
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio;
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
authors.affiliation: Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio; and.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.affiliation: Department of Medicine, University of Cincinnati, Cincinnati, Ohio; Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio david.d'alessio@duke.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: D'Alessio
mesh_terms: D052636:Allostasis; D000818:Animals; D001522:Behavior, Animal; D005247:Feeding Behavior; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism; D005934:Glucagon / Q000097:blood / Q000235:genetics / Q000378:metabolism; D018149:Glucose Intolerance / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006943:Hyperglycemia / Q000517:prevention & control; D007082:Ileum / Q000378:metabolism; D054795:Incretins / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007413:Intestinal Mucosa / Q000378:metabolism; D007515:Islets of Langerhans / Q000294:innervation / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism; D008297:Male; D062407:Meals; D009490:Neurosecretory Systems / Q000503:physiopathology*; D009928:Organ Specificity; D019518:Postprandial Period; D052336:Proglucagon / Q000235:genetics / Q000378:metabolism; D020318:Rats, Long-Evans
chemical_list: D054795:Incretins; D007328:Insulin; C549100:pro-glucose-dependent insulinotropic polypeptide; D052336:Proglucagon; D005749:Gastric Inhibitory Polypeptide; D005934:Glucagon
keywords: cephalic insulin secretion; glucose tolerance; insulin sensitivity; meal feeding; time-restricted feeding