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A B S T R A C T The aim of the present experiments was to determine the role of insulin and glucagon in the regulation of basal glucose production in dogs fasted overnight. A deficiency of either or both pancreatic hormones was achieved by infusing somatostatin (1 ug/kg per min), a potent inhibitor of both insulin and glucagon secretion, alone or in combination with intraportal replacement infusions of either pancreatic hormone. Infusion of somatostatin alone caused the arterial levels of insulin and glucagon to drop rapidly by 72+6 and 81±8%, respectively. Intraportal infusion of insulin and glucagon at rates of400 ,uU/kg per min and 1 ng/kg per min, respectively, resulted in the maintenance of the basal levels of each hormone. Glucose production was measured using tracer (primed constant infusion of [3-3H]glucose) and arteriovenous difference techniques.Isolated glucagon deficiency resulted in a 35+5% (P < 0.05) rapid and sustained decrease in glucose production which was abolished upon restoration ofthe plasma glucagon level. Isolated insulin deficiency resulted in a 52+16% (P < 0.01) increase in the rate of glucose production which was abolished when the insulin level was restored. Somatostatin had no effect on glucose production when the changes in the pancreatic hormone levels which it normally induces were prevented by simultaneous intraportal infusion of both insulin and glucagon.In conclusion, in the anesthetized dog fasted overThis work was presented in part at

A B S T R A C T The aim of the present experiments was to determine the effects of basal glucagon on glucose production after induction of prolonged insulin lack in normal conscious dogs fasted overnight. A selective deficiency of insulin or a combined deficiency of both pancreatic hormones was created by infusing somatostatin alone or in combination with an intraportal replacement infusion of glucagon. Glucose production (GP) When insulin deficiency was induced in the presence of basal glucagon the latter hormone caused GP to double and then to decline so that after 4 h it had returned to the control rate. The conversion of alanine and lactate into glucose, on the other hand, increased throughout the period of insulin lack. Withdrawal of glucagon after GP had normalized resulted in a 40% fall in GP, a 37% decrease in GNG, and a marked decrease in the plasma glucose concentration. Induction of insulin deficiency in the absence of basal glucagon resulted in an initial (30%) drop in GP followed by a restoration of normal GP after 2-3 h and moderately enhanced glucose formation from alanine and lactate.It can be concluded that (a) the effect of relative hyperglucagonemia on GP is short-lived; (b) the waning of the effect of glucagon is attributable solely to a diminution of glycogenolysis because GNG remains stimulated; (c)

The quantitative disposition of an intragastrically administered glucose load was studied in eight conscious 18-h fasted dogs using isotopic and arteriovenous (A-V) techniques. During the control period, the gut utilized 25% of the basal net hepatic glucose output (2.8 +/- 0.2 mg.kg-1.min-1). After glucose ingestion, 80% of the load was absorbed as glucose, 11% was converted across the gut to lactate and alanine, and 4% was oxidized to CO2. Two percent of the load remained in the gut 4 h after glucose administration and 3% was unaccounted for. During the absorptive period, net hepatic glucose balance (NHGB) varied considerably (mean range = output of 1.8 to uptake of 9.1 mg.kg-1.min-1), while endogenous hepatic glucose production (Ra hp) showed a consistent 80% suppression. The total net hepatic glucose uptake during the absorptive period (150 +/- 10 min) accounted for the disposal of 24 +/- 10% of the ingested load, and the amount of glucose escaping the splanchnic bed was 40 +/- 3%. Overall NHGB correlated positively with basal arterial glucose and insulin levels and negatively with basal arterial glycerol and FFA and with peak absorptive arterial glucose and insulin levels. These data suggest that the hepatic response to an ingested glucose load depends in part on the degree of metabolic fast of the animal at the time of glucose ingestion; the latter may be a major determinant of the roles played by the tissues in glucose disposal.

A B S T R A C T The effect of glucagon (50 ng/kg/min) on arterial glycerol concentration and net splanchnic production of total ketones and glucose was studied after an overnight fast in four normal and five insulin-dependent diabetic men. Brachial artery and hepatic vein catheters were inserted and splanchnic blood flow determined using indocyanine green. The glucagon infusion resulted in a mean circulating plasma level of 4,420 pg/mI.In the normal subjects, the glucagon infusion resulted in stimulation of insulin secretion indicated by rising levels of immunoreactive insulin and C-peptide immunoreactivity. Arterial glycerol concentration (an index of lipolysis) declined markedly and net splanchnic total ketone production was virtually abolished. In contrast, the diabetic subjects secreted no insulin (no rise in C-peptide immunoreactivity) in response to glucagon. Arterial glycerol and net splanchnic total ketone production in these subjects rose significantly (P = < 0.05) when compared with the results in four diabetics who received a saline infusion after undergoing the same catheterization procedure.Net splanchnic glucose production rose markedly during glucagon stimulation in the normals and diabetics despite the marked rise in insulin in the normals. Thus, the same level of circulating insulin which markedly suppressed lipolysis and ketogenesis in the normals failed to inhibit the glucagon-mediated increase in net splanchnic glucose production. It is concluded (a) that glucagon at high concentration is capable of stimulating lipolysis and ketogenesis in insulin-deficient diabetic man; (b) that insulin, mole for mole, has more antilipolytic activity in man than glucagon has lipolytic activity; and (c) that glucagon, on a molar basis, has greater stimulatory activity than insulin has inhibitory activity on hepatic glucose release.