Effects of two glucose absorption inhibitors: phenformin and 43–522 on hepatic gluconeogenesis

Abstract

The glucose absorption inhibitors, Phenformin and 3‐phenylpropylaminoguanide HCl (SaH 43–522) have different effects on hepatic gluconeogenesis. Unlike phenformin, 43–522 in vivo does not inhibit hepatic gluconeogenesis; inhibition occurred only when 43–522 was added directly to a liver perfusion system. This suggests that when 43–522 is administered in vivo it is metabolized to an agent that does not inhibit hepatic gluconeogenesis whereas phenformin is not metabolized, and does inhibit gluconeogenesis. This is an advantage of 43–522 since it thereby specifically inhibits intestinal glucose absorption without a potential hypoglycaemic effect due to the suppression of gluconeogenesis.

Effects of Metformin on Lactate Uptake and Gluconeogenesis in the Perfused Rat Liver

“…The acute nature of this effect suggests that this action on the liver may be a primary one in the generation of the chronic effects seen in vivo. The decrease in the net conversion is consistent with previous observations (22)(23)(24)(25)(26)(27)(28)(29) and mediated by changes in a number of fluxes. First, the flux from lactate to glucose is decreased.…”

“…Most notably with phenformin (28,29), but also to a small extent with other biguanides, elevations of lactate are seen with treatment. These two observations suggest that lactate metabolism may be the process principally affected by metformin.…”