Independance of glucagon and insulin handling by the isolated perfused dog kidney

Abstract

Summary. The effect of raising arterial plasma glucagon concentrations on kidney glucagon uptake was investigated using an isolated dog kidney perfused with whole blood. In addition, the effect of insulin on the magnitude of glucagon uptake by the kidney was studied at various glucagon concentrations. Renal vein plasma glucagon (V) has been found to be proportional to renal artery plasma glucagon (A). V and A were highly significantly correlated. In the absence of exogenous insulin infusion, V equalled 0.733 + 0.034 A, while in the presence of insulin V equalled 0.747 _+ 0.015 A. When kidney glucagon uptake was measured directly it increased as a function of arterial plasma glucagon. The calculated regression lines were similar in the presence and in the absence of insulin. The mean clearance rate of glucagon by the kidney was similar at low, medium or high concentrations of glucagon and was not affected by the presence of insulin at a mean concentration of 335.7 _+ 15.7 ~tU/ml. At this concentration of insulin, kidney insulin uptake was not affected by glucagon at concentrations ranging from 32 to 1600 pg/ml. Comparison of kidney glucagon uptake at similar arterial plasma glucagon concentrations, but with different renal plasma flows, indicated that kidney glucagon uptake is more dependant on arterial plasma glucagon concentration than on the quantity of glucagon entering the kidney per minute. It is concluded that." 1) kidney glucagon uptake increases as a function of arterial plasma glucagon concentration; 2) the clearance rate of glucagon is similar at low, medium or high arterial concentrations of glucagon; 3) at concentration of 300-350 gU/ml, insulin does not affect kidney glucagon uptake, and 4) at concentrations of glucagon up to 1600 pg/ml, renal insulin uptake is not affected by glucagon. These studies indicate that insulin and glucagon are handled independantly by the kidney of the dog.

Glucagon Metabolism in the Rat

“…In normal rats the arteriovenous IRG concentration difference averaged 22.9± 1.6%, a value quite siimiilar to that found in the dog (25%) by Lefebvre et al (23,27), but loxwer than the one described by Bastl et al (28) in rats (39%). In the latter study though, endogenous IRG release was not suippressed and renal vein canniulation imi-meidiately preceded blood collection for measurement of arterio-venous differences, this approach in our experience, causes substantial increments in plasma glucagoni levels and acute changes in renial hemodynamics, making extraction data difficult to interpret.…”

“…Kidney tissue contains specific glucagon-degrading enzymes in both the proximal tubular cytosol and brush border (25,26). Glucagoin is taken tip avidly by the autotransplanted as well as by the in vitro perfiused kidney of the dog (23,27) and by the rat kidney in situ (28). In animals, bilateral nephrectomy, uireteral ligation, or renal pediele-clamping lead promptly to hyperglucagoniemia (3,8,9,22,29,30).…”

Factors controlling gastric-glucagon release.

“…The sturgical procedure described here for the isolation of the stomiach can be carried otut witlhin 60-75 min by a sturgical team of two. The uise of a perfuision machinie, uitilizinig whole blood as a perfusion fluid and originally designed for the perfuision of isolated dog kidneys (16)(17)(18), permitted uis to study the function of this isolated dog stomach. Controls indicated perfect oxygenation of the blood throughout the experiment.…”

“…As previously shown necessary in this system (16), the blood was supplemented with 1,000 U/ml Trasylol (Bayer, Leverkusen, W. Germany). The perfusion system was essentially the one designed by Nizet and his co-workers for the perfusion of isolated dog kidneys (17,18); it consists basically of a film oxygenator and a Dale-Shuster pump under external hydraulic control.…”

“…The blood was equilibrated with a gaseous mixture containing 95% 02 and 5% CO2. The blood flow through the stomach was measured either by means of a side-branched graduated 25-ml pipette and temporary occlusion of the venous return, or directly by collecting the venous effluent in graduated cylinders (16). The arterial perfusion pressure in the isolated stomach was continuously measured with a mercury manometer and was adjusted if necessary by means of a Goldblatt clamp.…”