Metabolism of Insulin-I<sup>131</sup> and Glucagon-I<sup>131</sup> in the Kidney of the Rat

Narahara, H. T.; Everett, N. B.; Simmons, Barbara S.; Williams, R. E. O.

doi:10.1152/ajplegacy.1958.192.2.227

Cited by 51 publications

(23 citation statements)

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“…As previously demonstrated [1], the urinary clearance of glucagon represents only a small percentage of the clearance of glucagon by the kidney. 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].…”

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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“…This was confirmed with the immunoperoxidase technique. Although these findings have not been reported for PTH, localization of insulin (33)(34)(35), glucagon (36), growth hormone (37)(38)(39), luteinizing hormone, and follicle-stimulating hormone (40,41), human chorionic gonadotropin (42), and prolactin (43) (13), and our current data-showing that localization of 125I-labeled and unlabeled preparations are identical, indicate that the metabolism ofthe radioiodinated PTH used in these studies accurately reflects the metabolism of unlabeled hormone.…”

Section: Discussioncontrasting

confidence: 53%

Analysis of Parathyroid Hormone and Its Fragments in Rat Tissues

D'Amour¹,

Segre²,

Roth³

et al. 1979

J. Clin. Invest.

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A B S T R A C T After intravenous injection of [125LI]iodo-parathyroid hormone in the rat, uptake of the hormone was greatest in the liver and kidneys. Uptake was rapid, reaching a maximal concentration by 4 and 8 min, respectively. Extracts, prepared from both these organs at intervals soon after the injection of intact hormone, showed three main radioactive peaks when samples were subjected to gel filtration under proteindenaturing conditions. The first peak coeluted with intact hormone.The second eluted at a position corresponding to the carboxy-terminal fragments previously described in plasma, and the last eluted at the salt volume of the column. Microsequence analysis of the radioiodinated fragments, a method that has proved valuable for chemically defining the circulating fragments resulting from metabolism of injected hormone, showed that extracts of liver and kidney, prepared at 4 and 8 min after injection of the intact hormone, contained different fragments. The radioiodinated fragments in liver extracts were identical to those previously reported in the plasma of rats and dogs, fragments resulting principally from proteolysis between positions 33 and 34, and 36 and 37 of the intact hormone. Although the same fragments were also present in the kidneys, they constituted less than 15% of the amount present in the liver. More than 50% of the

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“…The renal handling of proinsulin, insulin, and C-peptide was characterized by high extraction rates and very low urinary clearances, indicating that almost all the polypeptide removed from the circulation was sequestered or metabolized in the kidney. Kidney homogenates are known to destroy insulin in vitro (11,32), and autoradiographic studies in the rat show that labeled insulin accumulates in the cells of the proximal convoluted tubules (33,34), where it presumably undergoes degradation. It is of interest that other small molecular weight polypeptides are handled by the kidney in similar fashion.…”

Section: Resultsmentioning

confidence: 99%

Metabolism of Proinsulin, Insulin, and C-Peptide in the Rat

Katz¹,

Rubenstein²

1973

J. Clin. Invest.

256

121

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A B S T R A C T The renal extraction and excretion of bovine proinsulin, insulin, and C-peptide and the contribution of the kidney to their total metabolic clearance rate (MCR) were studied in the rat. Metabolic clearance rates were measured by the constant infusion technique and plasma and urine concentrations of each polypeptide were determined by radioimmunoassay.The MCR of insulin (16.4±0.4 ml/min) was significantly greater than that of either proinsulin (6.7 ±0.3 ml/min) or C-peptide (4.6±0.2 ml/min). Metabolic clearance rates were independent of plasma levels over a range of steady-state plasma concentrations varying from 1 to 15 ng/ml.In contrast to the differences in their metabolic clearance rates, the renal disposition of the three polypeptides was similar, being characterized by high extraction and very low urinary clearance. The renal arteriovenous difference of proinsulin, insulin, and C-peptide averaged 36, 40, and 44%, respectively, and was linearly related to their arterial concentration between 2 and 25 ng/ml. When glomerular filtration was markedly reduced or stopped by ureteral obstruction, the renal extraction of proinsulin, insulin, and C-peptide was invariably greater than the simultaneously measured extraction of inulin, indicating that these polypeptides are removed from the renal circulation by both glomerular filtration and direct uptake from peritubular capillary blood. The fractional urinary clearance of each polypeptide never exceeded 0.6%, indicating that more than 99% of the amount filtered was sequestered in the kidney.The renal removal of proinsulin and C-peptide from the circulation accounts for 55 and 69% of their metabolic clearance rates, while the renal contribution to the peripheral metabolism of insulin was smaller, averThis work was published in abstract form in 1972 J. Clin. Invest. 51: 49a.Received for publication 18 September 1972 and in revised form 13 December 1972. aging 33%. This difference is due to the fact that insulin, but not the other two polypeptides, is metabolized to a significant extent by the liver. These results define the renal handling of proinsulin, insulin, and Cpeptide in the rat and indicate that in this species the kidney represents a major site for insulin metabolism and is the main organ responsible for the degradation of proinsulin and C-peptide. INTRODUCTIONDifferential secretion rates of insulin, proinsulin, and C-peptide by pancreatic beta cells have generally been considered to be the major determinant of their plasma concentrations (1-3). However, in vivo and in vitro studies have indicated that the peripheral distribution, metabolism, and degradation of insulin and proinsulin differ, suggesting that these factors may play an important role in determining their blood levels. Thus, the half disappearance time of proinsulin in dogs (4), swine (5), rats (6), and baboons (5) is two-to threefold longer than that of insulin. Experiments with the isolated perfused liver (7,8) have shown a high clearance of insulin compared with the removal...

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Metabolism of Insulin-I¹³¹ and Glucagon-I¹³¹ in the Kidney of the Rat

Cited by 51 publications

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

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

Analysis of Parathyroid Hormone and Its Fragments in Rat Tissues

Metabolism of Proinsulin, Insulin, and C-Peptide in the Rat

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Metabolism of Insulin-I131 and Glucagon-I131 in the Kidney of the Rat

Cited by 51 publications

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

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

Analysis of Parathyroid Hormone and Its Fragments in Rat Tissues

Metabolism of Proinsulin, Insulin, and C-Peptide in the Rat

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Metabolism of Insulin-I¹³¹ and Glucagon-I¹³¹ in the Kidney of the Rat