title: Induction of control genes in intestinal gluconeogenesis is sequential during fasting and maximal in diabetes.
abstract: We studied in rats the expression of genes involved in gluconeogenesis from glutamine and glycerol in the small intestine (SI) during fasting and diabetes. From Northern blot and enzymatic studies, we report that only phosphoenolpyruvate carboxykinase (PEPCK) activity is induced at 24 h of fasting, whereas glucose-6-phosphatase (G-6-Pase) activity is induced only from 48 h. Both genes then plateau, whereas glutaminase and glycerokinase strikingly rebound between 48 and 72 h. The two latter genes are fully expressed in streptozotocin-diabetic rats. From arteriovenous balance and isotopic techniques, we show that the SI does not release glucose at 24 h of fasting and that SI gluconeogenesis contributes to 35% of total glucose production in 72-h-fasted rats. The new findings are that 1) the SI can quantitatively account for up to one-third of glucose production in prolonged fasting; 2) the induction of PEPCK is not sufficient by itself to trigger SI gluconeogenesis; 3) G-6-Pase likely plays a crucial role in this process; and 4) glutaminase and glycerokinase may play a key potentiating role in the latest times of fasting and in diabetes.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale 449, Faculté Laennec, 69372 Lyon, France. mithieux@laennec.univ-lyon1.fr
authors.forename: Gilles
authors.initials: G
authors.lastname: Mithieux
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bady
authors.forename: Amandine
authors.initials: A
authors.lastname: Gautier
authors.forename: Martine
authors.initials: M
authors.lastname: Croset
authors.forename: Fabienne
authors.initials: F
authors.lastname: Rajas
authors.forename: Carine
authors.initials: C
authors.lastname: Zitoun
mesh_terms: D000818:Animals; D003920:Diabetes Mellitus / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation; D005215:Fasting / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005943:Gluconeogenesis; D005947:Glucose / Q000096:biosynthesis; D005952:Glucose-6-Phosphatase / Q000235:genetics / Q000378:metabolism*; D005972:Glutaminase / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D005991:Glycerol Kinase / Q000235:genetics / Q000378:metabolism*; D007421:Intestine, Small / Q000201:enzymology*; D008297:Male; D008657:Metabolic Clearance Rate; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
chemical_list: D005973:Glutamine; D005991:Glycerol Kinase; D005952:Glucose-6-Phosphatase; D005972:Glutaminase; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose; D005990:Glycerol