PEPCK is a key enzyme of gluconeogenesis in liver and kidney. Recently, we
have shown that small intestine also contributes to the endogenous glucose
production in insulinopenia in rats and that glutamine is the main precurso
r of glucose synthesized in this tissue. The expression of the PEPCK gene i
n rat and human small intestine and the effect of streptozotocin-induced di
abetes and fasting have been studied using reverse transcriptase-polymerase
chain reaction, Northern blot analysis, and determination of enzyme activi
ty. The PEPCK gene is expressed along the whole small intestine in adult ra
t and human. The abundance of PEPCK mRNA was increased similar to 30 times
in the duodenum, 15 times in the jejunum, and only 3 times in the ileum fro
m diabetic rats. PEPCK mRNA was downregulated in all parts of the tissue up
on insulin treatment for 10 h. In 48-h fasted rats, the PEPCK mRNA abundanc
e was increased 17 times in the duodenum and the jejunum and 3 times in the
ileum, and it was normalized upon refeeding for 7 h. PEPCK activity was al
so increased 2-5 times in diabetic and fasted rats in the duodenum and jeju
num but not in the ileum. We conclude that PEPCK is a crucial enzyme contri
buting to the induction of gluconeogenesis in small intestine, just as it i
s well known to be in the liver and kidney.