Induction of control genes in intestinal gluconeogenesis is sequential during fasting and maximal in diabetes

• Published in: American journal of physiology: endocrinology and metabolism 2004-03, Vol.286 (3), p.E370-E375
• Main Authors: Mithieux, Gilles, Bady, Isabelle, Gautier, Amandine, Croset, Martine, Rajas, Fabienne, Zitoun, Carine
• Format: Article
• Language: English
• Subjects: Animals; Diabetes Mellitus - enzymology; Diabetes Mellitus - genetics; Enzyme Activation; Fasting - metabolism; Gene Expression Regulation, Enzymologic; Gluconeogenesis; Glucose - biosynthesis; Glucose-6-Phosphatase - genetics; Glucose-6-Phosphatase - metabolism; Glutaminase - genetics; Glutaminase - metabolism; Glutamine - metabolism; Glycerol - metabolism; Glycerol Kinase - genetics; Glycerol Kinase - metabolism; Intestine, Small - enzymology; Male; Metabolic Clearance Rate; Phosphoenolpyruvate Carboxykinase (ATP) - genetics; Phosphoenolpyruvate Carboxykinase (ATP) - metabolism; Rats; Rats, Sprague-Dawley; Tissue Distribution
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.00299.2003

Institut National de la Santé et de la Recherche Médicale 449, Faculté Laennec, 69372 Lyon, France Submitted 1 July 2003 ; accepted in final form 9 October 2003 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 phospho enol pyruvate 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. glucose-6-phosphatase; phospho enol pyruvate carboxykinase; glutaminase; glycerokinase Address for reprint requests and other correspondence: G. Mithieux, INSERM 449, Faculté Laennec, 69372 Lyon, cedex 08, France (e-mail: mithieux{at}laennec.univ-lyon1.fr ).