The role of CCK8 in the inhibition of glucose production.

A recent study suggested that a rise of cholecystokinin (CCK8) in the duodenum may bring about an inhibition of hepatic glucose production. The authors made use of the pancreatic clamp technique to characterize a gut-brain-liver signal generated by CCK8 that reduces glucose output by the liver. The pancreatic clamp conditions used created a situation in which the liver was markedly deficient in both insulin and glucagon. Although the data presented indicated that CCK8 can reduce glucose production, the authors do not establish a role for this inhibition in the reduction of glucose output seen in response to feeding. It must be remembered that in response to a meal the insulin level in the hepatic sinusoids rises markedly, as does the insulin level to which the brain is exposed. It therefore seems likely that either or both of these effects will drive the suppression of glucose production rather than any effect of CCK8. The importance of the CCK8 effect needs to be determined in the presence of elevated arterial and sinusoidal insulin before any conclusion can be drawn about its relevance.