After trauma or sepsis, the liver undergoes a reprioritization of export protein synthesis with elevated production of some acute-phase reactants and reduced production of others. We have examined the effects of combinations of insulin and the counterregulatory hormones (dexamethasone, glucagon, and epinephrine), in the presence or absence of interleukin (IL)-6, on the production by isolated hepatocytes of the positive acute-phase proteins C-reactive protein, alpha 1-antichymotrypsin, alpha 1-acid glycoprotein, and haptoglobin, and the negative acute-phase proteins prealbumin and transferrin. The effect of IL-6 on the production of the above proteins was influenced significantly by insulin and all of the counterregulatory hormones. Significant three-way interactions as well as higher order interactions between the stress hormones and insulin were seen in the case of C-reactive protein. The results indicate that both positive and negative acute-phase proteins respond differently to insulin and the counterregulatory hormones and that the potential exists for the regulation of synthesis of individual acute-phase reactants by interaction between the cytokine network and the classical endocrine hormones.

No abstract

Insulin hypoglycaemia provides a glycopenic stimulus producing a vagal gastric secretory response (Jogi, Strom, and Uvnas, 1949). Earlier investigators (Hollander, Jemerin, and Weinstein, 1942;Davis, Brooks, and Robert, 1965) believed that the gastric acid response to insulin hypoglycaemia represented an 'all-or-none' phenomenon which was (1) initiated when the blood glucose fell to a given threshold value and (2) not related to the degree of hypoglycaemia below such a threshold. The recent finding, however, of a quantitative relationship between insulin dose, hypoglycaemia, and acid secretion (Baron, 1970;Spencer and Grossman, 1971) does not support the 'all-or-none' hypothesis.A single rapid intravenous injection of insulin, such as used by the previously mentioned workers, produces a nadir of hypoglycaemia with gradual restoration of normoglycaemia. In human subjects (Carter, Dozois, and Kirkpatrick, 1972) an infusion of insulin provides a steady level of hypoglycaemia which, if reproducible in the dog, should facilitate correlation studies between blood glucose changes and gastric acid changes.The present investigation was undertaken to study the effect of a continuous infusion of insulin on the blood glucose response in the dog and to establish the relationship between insulin dose, degree of hypoglycaemia, and acid response.