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Am J Physiol Endocrinol Metab (October 14, 2003). doi:10.1152/ajpendo.00299.2003
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Submitted on July 1, 2003
Accepted on October 9, 2003

THE INDUCTION OF CONTROL GENES IN INTESTINE GLUCONEOGENESIS IS SEQUENTIAL DURING FASTING AND MAXIMAL IN DIABETES

Gilles Mithieux1*, Isabelle Bady1, Amandine Gautier1, Martine Croset1, Fabienne Rajas1, and Carine Zitoun1

1 Faculte Laennec, INSERM 449, Lyon, France

* To whom correspondence should be addressed. E-mail: mithieux{at}laennec.univ-lyon1.fr.

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 the PEPCK activity is induced at 24h of fasting, whereas the glucose-6 phosphatase (Glc6Pase) activity is induced from 48h only. Both genes then plateau, whereas glutaminase and glycerokinase strikingly rebound between 48h and 72h. 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 24h of fasting and that SI gluconeogenesis contributes to 35% of total glucose production in 72h-fasted rats. The new findings are: 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) Glc6Pase likely plays a crucial role in this process; 4) glutaminase and glycerokinase may play a key potentiating role in the latest times of fasting and in diabetes.




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