Failure of Somatostatin to Modify Effect of Glucagon on Carbohydrate Metabolism in the Dog

Somatostatin is widely used to inhibit insulin and glucagon release by the pancreas in studies of metabolic regulation in vivo. To determine whether the peptide can directly modify the metabolic effects of an increment in glucagon in overnight-fasted conscious dogs, glucagon was increased in the presence (+S) or absence (-S) of somatostatin. Either somatostatin (+S; 0.8 microgram . kg-1 . min-1) or a two-stage pancreatectomy (-S) was used to inhibit the endocrine pancreas, and at the same time replacement infusions of insulin (285-300 microU . kg-1 .min-1) and glucagon (0.65 ng . kg-1 . min-1) were given. After a 40-min control period the plasma glucagon level was raised fourfold in the presence of fixed basal insulin. Plasma insulin in both groups were similar [11 +/- 2 (+S) and 9 +/- 1 (-S) microU/ml]. Glucagon rose from 64 +/- 11 to 225 +/- 19 and 92 +/- 11 to 219 +/- 20 pg/ml in the +S and -S groups, respectively. Tracer-determined ([3-3H]glucose) glucose production rose by 5.28 +/- 1.02 (+S) and 4.25 +/- 1.12 (-S) mg . kg-1 . min-1 at 15 min and fell similarly over 3 h in both groups. Plasma glucose rose similarly in both groups peaking at 195 +/- 15 (+S) and 174 +/- 8 (-S) mg/dl. Plasma alanine fell similarly over 3 h [133 +/- 35 (+S) and 138 +/- 42 (-S) mumol/liter]. Conversion of [14C]alanine and [14C]-lactate to [14C]glucose rose progressively over 3 h in both groups, eventually being elevated by 210 +/- 58 (+S) and 148 +/- 48% (-S). We conclude that in the dog somatostatin at the dose used does not alter the effect of an increment in glucagon on carbohydrate metabolism.