Effect of verapamil on basal and glucagon-dependent splanchnic glucose metabolism and insulin secretion in man.

To determine the effect of verapamil on basal and glucagon-induced changes in splanchnic glucose metabolism and insulin secretion, six healthy men were studied during a primed-continuous infusion of verapamil (2.5 micrograms/kg/min). After a basal period of 30 min, glucagon was infused at a rate of 12 ng/kg/min for an additional 60 min. Splanchnic exchange of glucose, lactate, alanine and beta-hydroxy-butyrate, as well as splanchnic C-peptide release, reflecting insulin production rate, were determined by means of the liver vein catheter technique. Intraindividual control trials without verapamil were performed. Basal and glucagon-stimulated arterial glucose and insulin concentrations as well as insulin production rate were not significantly altered by verapamil, which also had no influence on basal splanchnic glucose output or on the glucagon-induced initial (0-30 min) increment in splanchnic glucose output. However, the gradual decline in splanchnic glucose output was delayed at 30-60 min (verapamil: 55.85 +/- 6.31 control: 39.73 +/- 5.6 mmol/30 min; mmol/30 min, mean, s.e.m., p less than 0.02). Splanchnic lactate-alanine- and beta-hydroxy-butyrate exchange were also unchanged by verapamil. We conclude that verapamil attenuates glucagon's evanescent effect on splanchnic glucose output without interfering with the exchange of gluconeogenic precursors or beta-hydroxy-butyrate or insulin production rate.