RATES OF GLUCAGON ACTIVATION AND DEACTIVATION OF HEPATIC GLUCOSE-PRODUCTION IN CONSCIOUS DOGS

To determine the time course of glucagon activation and deactivation o f hepatic glucose production (HGP), studies were conducted in 18-hour fasted, conscious dogs. Somatostatin was infused with insulin replaced intraportally at 1.8 pmol.kg(-1).min(-1) and glucagon replaced periph erally at 1.0 ng.kg(-1).min(-1). After a 2-hour control period, glucag on infusion was either (1) increased fourfold for 4 hours (GGN 4X), (2 ) increased fourfold for 30 minutes and returned to a basal rate for 3 .5 hours (GGN 4X/1X), or (3) fixed at the basal rate for 4 hours (GGN 1X). In the latter two protocols, glucose was infused peripherally to match glucose concentrations observed during GGN 4X, Glucose turnover was determined by deconvolution with the impulse response of the gluco se system described by a two-compartment, time-varying model identifie d from high-performance liquid chromatography (HPLC)-purified [3-H-3]g lucose tracer data, In GGN 4X, HGP was stimulated from 15.2 +/- 0.9 mu mol.kg(-1).min(-1) to 52.7 +/- 6.5 mu mol.kg(-1).min(-1) after just 1 5 minutes, but it decreased over the subsequent 3 hours to a rate 25% above basal. In GGN 4X/1X, the increase in HGP during the first 30 min utes equaled that observed in GGN 4X, but when glucagon infusion was r eturned to basal, HGP decreased in 15 minutes to rates equal to those observed in GGN 1X. The times for half-maximal activation and deactiva tion of glucagon action were equal (4.5 +/- 1.0 and 4.0 +/- 1.1 minute s, respectively). The very rapid and sensitive hepatic response to glu cagon makes pancreatic glucagon release a key component of minute-to-m inute glucose homeostasis. Copyright (C) 1998 by W.B. Saunders Company .