Effects of VIP and forskolin on alanine metabolism in isolated hepatocytes.

The effects of vasoactive intestinal polypeptide (VIP) and of forskolin on alanine metabolism in hepatocytes isolated from fed and fasted rats were examined. VIP and 17 microM forskolin stimulated glucose production, gluconeogenesis from alanine, and ureagenesis, and inhibited glyconeogenesis to comparable degrees. However, combination of 17 microM forskolin with a maximal dose of VIP significantly augmented only the inhibition of glyconeogenesis. At 100 microM, forskolin induced metabolic responses comparable to those induced by glucagon, but similarly, in combination with maximal doses of VIP or glucagon, augmented only inhibition of glycogen synthesis. In addition to demonstrating modulation of alanine metabolism by VIP and forskolin, these results raise questions about the nature of the coupling between VIP receptor occupancy and metabolic response.