Role of the Kidney in the Disposal of Radioiodinated and Nonradioiodinated Insulin in Dogs

Zaharko, Daniel S.; Beck, Lyle V.; Blankenbaker, Ronald

doi:10.2337/diab.15.9.680

Cited by 38 publications

(21 citation statements)

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“…This observation is in agreement with earlier data which demonstrated that glucagon may be filtered through the glomerulus and reabsorbed at the tubular level [ 13]. This does not however exclude the possibility of a direct uptake from renal capillaries without previous filtration and reabsorption, as has been demonstrated for insulin [14][15]. The existence of such mechanism is supported by our finding that renal clearance rate of glucagon may be higher than the glomerular filtration rate.…”

Section: Insulin Uptake By the Kidney At Various Arterial Concentratisupporting

confidence: 92%

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

1976

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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.

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Section: Insulin Uptake By the Kidney At Various Arterial Concentratisupporting

confidence: 92%

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

1976

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“…However, there are only a relatively few papers dealing with the quantitative effects of kidney disease on insulin degradation (22)(23)(24), and these studies seem to suffer from certain defects. In the first place, disappearance of nonspecific trichloroacetic acid (TCA)-precipitable radioactivity has been followed, despite the fact that several authors have indicated that this method does not adequately separate intact immunoprecipitable insulin from its labeled degradation products (25)(26)(27). Secondly, the use of this technique would have the effect of accentuating the already curvilinear insulin-'I disappearance curve and make less justifiable the use of analytical techniques appropriate only for first order processes.…”

Section: Discussionmentioning

confidence: 99%

Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Silvers¹,

Swenson²,

Farquhar³

et al. 1969

J. Clin. Invest.

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Veterans Administration Hospital, Palo Alto, California 94305 AB S T R A C T Insulin-LuI was administered intravenously to normal subjects, to patients with maturityonset diabetes and normal renal function, and to nondiabetic patients with renal failure. The ensuing plasma disappearance curves of immunoprecipitable radioactive insulin were determined, and these data were analyzed in a variety of ways. Firstly, fractional irreversible loss rates of insulin from plasma were calculated and found to be greatly diminished in patients with renal failure (t4 = 39 min), as compared with normal (t4 = 15 min) and diabetic subjects (ti = 12 min). Secondly, plasma insulin-2'I disappearance curves were resolved into sums of three exponentials by the method of "peeling," and values for the resultant three slopes and half-lives were determined. Patients with normal renal function had similar values for all parameters, while those patients with renal failure were differentiated on the basis of the slope of the last component, with a prolongation of its half-life to 275 min (approximately twice normal). Finally, a three pool model was formulated to describe the kinetics of plasma insulin disappearance in man. representing plasma (pool 1), interstitial fluid (pool 2), and all tissues in which insulin is utilized and degraded (pool 3). The proposed model adequately describing the disappearance curves of insulin-'I observed in all patients indicated that volumes (per cent body weight) of pool 1 (4.04) and pool 2 (10.11), calculated on the basis of the model and the experimental data, corresponded closely to estimates of plasma and interstitial fluid vol- umes obtained by independent means. It also demonstrated that patients with renal failure were characterized by a decreased removal rate of insulin from pool 3 and an increased recycling rate of insulin from pool 3 to pool 2. It is concluded that the proposed model represents a reasonable description of the kinetics of insulin distribution and degradation, and that its use provides quantitative insights into the physiology of insulin metabolism.

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“…This small difference is not measurable by the technique used by us. Thus, even if the permeability of the glomerulus to Zn-a2 far exceeds that to albumin, it is much lower than that to the low-molecular-weight proteins usually studied, some of which have renal extraction rates approaching or exceeding the filtration fraction (36)(37)(38)(39)(40)(41).…”

Section: Introductionmentioning

confidence: 99%

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein.

Ekman¹,

Johansson²,

Ravnskov³

1976

J. Clin. Invest.

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Role of the Kidney in the Disposal of Radioiodinated and Nonradioiodinated Insulin in Dogs

Cited by 38 publications

References 0 publications

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

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

Derivation of a three compartment model describing disappearance of plasma insulin-131I in man

Renal handling of Zn-alpha2-glycoprotein as compared with that of albumin and the retinol-binding protein.

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