title: Intracerebroventricular infusion of a triglyceride emulsion leads to both altered insulin secretion and hepatic glucose production in rats.
abstract: We investigated here whether non-esterified fatty acids (NEFA) influence insulin secretion and action through a direct effect on central nervous system sites involved in the control of glucose homeostasis. Normal Wistar rats received a 48-h intracerebroventricular infusion of either a 10% triglyceride (Intralipid, IL)/heparin emulsion (IL/h) or saline/heparin solution (control). At 48 h, insulin secretion as measured by an intravenous glucose tolerance test, was more elevated in IL/h than in control rats. Pancreatic noradrenaline turnover was decreased by 57% in IL/h rats, suggesting low pancreatic sympathetic output that could account partly for the elevated insulin secretion. The time course of glycaemia was similar in both groups, suggesting insulin resistance. Euglycaemic-hyperinsulinaemic clamps were imposed to assess peripheral and hepatic insulin sensitivity. At each insulin concentration glucose utilization was increased to a similar extent in both groups, whereas hepatic glucose production decreased much less in IL/h than in control rats. Hepatic insulin insensitivity could be related partly to activation of the hypothalamic-pituitary-adrenocortical axis, since plasma corticosterone concentration was significantly increased in IL/h rats compared with controls. Our data indicate that lipids may alter both insulin secretion and hepatic sensitivity to insulin through their effect on central nervous system.
authors.affiliation: Laboratoire de Physiopathologie de la Nutrition, Université Paris 7-Denis Diderot, CNRS UMR 7059, case 7126, 2, place Jussieu, 75251 Paris cedex 05, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Clément
authors.forename: Céline
authors.initials: C
authors.lastname: Cruciani-Guglielmacci
authors.forename: Christophe
authors.initials: C
authors.lastname: Magnan
authors.forename: Mylène
authors.initials: M
authors.lastname: Vincent
authors.forename: Laetitia
authors.initials: L
authors.lastname: Douared
authors.forename: Martine
authors.initials: M
authors.lastname: Orosco
authors.forename: Françoise
authors.initials: F
authors.lastname: Assimacopoulos-Jeannet
authors.forename: Luc
authors.initials: L
authors.lastname: Pénicaud
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
mesh_terms: D000818:Animals; D001769:Blood / Q000378:metabolism; D001812:Blood-Brain Barrier; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage*; D005947:Glucose / Q000096:biosynthesis*; D015309:Glucose Clamp Technique; D007276:Injections, Intraventricular; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D010168:Palmitates / Q000493:pharmacokinetics; D010179:Pancreas / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D005217:Fat Emulsions, Intravenous; D007328:Insulin; D010168:Palmitates; D005947:Glucose; D009638:Norepinephrine