No abstract

We undertook studies in conscious dogs to assess the role of basal glucagon in stimulating glucose production after a 7-day fast. Two protocols consisting of a 40-min basal period (-40 to 0 min), and a 180-min test period (0-180 min) were used. During the test period of the first protocol (hormone replacement; n = 4), somatostatin was infused (0.8 micrograms.kg-1.min-1) along with basal intraportal replacement amounts of insulin and glucagon, whereas in the second protocol (glucagon deficiency; n = 5), somatostatin plus insulin alone were infused. Glucose production and gluconeogenesis were measured using tracer and arteriovenous difference techniques. Plasma insulin levels were similar during the test period in both protocols (6 +/- 1 microU/ml). The plasma immunoreactive glucagon level in the control protocol averaged 50 +/- 8 pg/ml, whereas in the glucagon-deficiency protocol the level fell from 50 +/- 8 to 29 +/- 8 pg/ml (P less than 0.05). The plasma glucose level and the rate of glucose production were unchanged during bihormonal replacement. During glucagon deficiency the plasma glucose level was held constant at 100 +/- 4 mg/dl by glucose infusion. Tracer-determined endogenous glucose production fell from 1.8 +/- 0.1 to 1.0 +/- 0.1 mg.kg-1.min-1 by 30 min (P less than 0.05). After 3 h of glucagon deficiency, gluconeogenic conversion of alanine to glucagon was reduced 40% and the hepatic fractional extraction of alanine was reduced by 45%. The efficiency of the gluconeogenic process within the liver was not altered by glucagon deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)

A B S T R A C T The renal handling of' the biologically active glucagon component (the 3,500-mol wt fraction of immunoreactive glucagon [IRG]) and the contribution of the kidney to its overall peripheral metabolism were studied in normal and uremic rats. The metabolic clearance rate of glucagon was 31.8 ± 1.2 ml/min per kg in normal animals and was diminished by approximately one-third in each of three groups of rats with compromized renal ftinction:22.3+1.6 ml/min per kg in partially (70%) nephrectomized; 22.9±3.3 ml/min per kg in bilaterally ureteral ligated; and 23.2± 1.2 ml/min per kg in bilaterally nephrectomized animals. In normal rats the kidney contributed 30% to the overall metabolic clearance of the hormone and the renal extraction of endogenous and exogenous glucagon was similar, averaging 22.9±1.6% and was independent of plasma IRG levels over a wide range of arterial concentrations. The remnant kidney of partially (70%) nephrectomized aniimals continued to extract substantial amounts (16.6±4.2%) of the hormone, but accounted for only 8% of the total peripheral catabolism of' IRG. In the two groups of' animals with filtering kidneys, renal glucagon uptake was linearly related to its filtered load and could be accounted for by glomerular filtration and tubuilar reabsorption. However, the kidneys of animals with both ureters ligated (renal extraction of' inulin = 3.2±1.8%) and hence virtual absence of glomiiertilar filtration, continuied to extract 11.5±1.9% of the renal arterial glucagon, contributing by 9% to its overall metabolic clearanee, indicating that IRG uptake occurs also from the post glomerular capillaries.