Glucose-6-phosphatase mRNA levels in kidney isolated tubule suspensions are increased by dexamethasone and decreased by insulin.
The strong induction of renal glucose-6-phosphatase (G6Pase) during starvation has been suggested to be responsible for the increased role of the kidney in glucose production during long-term fasting. To investigate whether this induction may be caused by a direct hormonal effect on the renal proximal tubular cell, we incubated rat renal tubule suspensions in the presence of glucocorticoids or insulin for 6 hours; normoxia was required, since hypoxic conditions were associated with markedly decreased G6Pase mRNA levels despite maintenance of adenosine triphosphate (ATP) levels. The G6Pase mRNA level was increased twofold to threefold by 10(-8) to 10(-5) mol/L dexamethasone (DXM), whereas the most effective concentration of insulin, 10(-9) mol/L, induced only a 40% decrease. These results suggest that the increased role of the kidney in glucose production during long-term starvation could be linked to a direct effect of glucocorticoids on renal G6Pase.
Simonnet
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Laboratoire Mécanismes Moléculaires du Diabète, Institut National de la Santé et de la Recherche Médicale, U449, Faculté de Médecine Laënnec, Lyon, France.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005952:Glucose-6-Phosphatase / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology*; D007684:Kidney Tubules / Q000201:enzymology*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation
D000893:Anti-Inflammatory Agents; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D003907:Dexamethasone; D005952:Glucose-6-Phosphatase