Is There Glucose Production Outside of the Liver and Kidney?

This review analyzes the evidence presented to support the role of organs other than the liver and kidney to release substantial amounts of glucose into the mammalian blood circulation. The evidence includes (a) the identification of gluconeogenic enzyme activities in various organs, especially the small intestine, (b) levels of mRNA for the same enzymes, and (c) measurements of gluconeogenic flux in the small intestine. The latter would be the definite proof of extrahepatic, extrarenal glucose production. We critically evaluate the radioactive and stable isotopic techniques used to measure intestinal gluconeogenesis. We also simulate the impact of unavoidable measurement errors on apparent rates of intestinal gluconeogenesis. We conclude that there is so far no credible evidence to support the concept that glucose can be produced by the intestine or by muscle.