title: Feeding a protective hydrolysed casein diet to young diabetic-prone BB rats affects oxidation of L[U-14C]glutamine in islets and Peyer's patches, reduces abnormally high mitotic activity in mesenteric lymph nodes, enhances islet insulin and tends to normalize NO production.
abstract: The present studies were undertaken to examine concomitant diet-induced changes in pancreatic islets and cells of the gut immune system of diabetes-prone BB rats in the period before classic insulitis. Diabetes-prone (BBdp) and control nondiabetes prone (BBc) BB rats were fed for approximately 17 days either a mainly plant-based standard laboratory rodent diet associated with high diabetes frequency, NIH-07 (NIH) or a protective semipurified diet with hydrolyzed casein (HC) as the amino acid source. By about 7 weeks of age, NIH-fed BBdp rats had lower plasma insulin and insulin/glucose ratio, lower insulin content of isolated islets, lower basal levels of NO but higher responsiveness of NO production to IL-1beta in cultured islets, and higher Con A response and biosynthetic activities in mesenteric lymphocytes than control rats fed the same diet. In control rats, the HC diet caused only minor changes in most variables, except for a decrease in oxidation of L-[U-14C]glutamine in Peyer's patch (PP) cells and an increase in protein biosynthesis in mesenteric lymphocytes. In BBdp rats, however, the HC diet increased plasma insulin concentration, islet insulin/protein ratio, and tended to normalize the basal and IL-1beta-stimulated NO production by cultured islets. The HC diet decreased oxidation of L[U-14C]glutamine in BBdp pancreatic islets, whereas oxidation of L-[U-14C]glutamine in PP cells was increased, and the basal [Methyl-3H]thymidine incorporation in mesenteric lymphocytes was decreased. These findings are compatible with the view that alteration of nutrient catabolism in islet cells as well as key cells of the gut immune system, particularly changes in mitotic and biosynthetic activities in mesenteric lymphocytes, as well as basal and IL-1beta stimulated NO production, participate in the sequence of events leading to autoimmune diabetes in BB rats. Thus, the protection afforded by feeding a hydrolysed casein-based diet derives from alterations in both the target islet tissue and key cells of the gut immune system in this animal model of type 1 diabetes.
authors.affiliation: Laboratory of Experimental Medicine, Brussels Free University, Belgium.
authors.forename: W J
authors.initials: WJ
authors.lastname: Malaisse
authors.forename: E
authors.initials: E
authors.lastname: Olivares
authors.forename: A
authors.initials: A
authors.lastname: Laghmich
authors.forename: L
authors.initials: L
authors.lastname: Ladrière
authors.forename: A
authors.initials: A
authors.lastname: Sener
authors.forename: F W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000284:Administration, Oral; D000821:Animal Feed; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology*; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D004044:Dietary Proteins; D004195:Disease Models, Animal; D005260:Female; D005973:Glutamine / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D008198:Lymph Nodes / Q000166:cytology*; D008297:Male; D008938:Mitosis; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D010581:Peyer's Patches / Q000378:metabolism*; D011492:Protein Hydrolysates / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011913:Rats, Inbred BB; D012016:Reference Values; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D002364:Caseins; D004044:Dietary Proteins; D007328:Insulin; D011492:Protein Hydrolysates; C026375:trypticase-soy broth; D005973:Glutamine; D009569:Nitric Oxide