Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Samols, Ellis; Ryder, Jill A.

doi:10.1172/jci104435

Cited by 136 publications

(42 citation statements)

References 21 publications

(24 reference statements)

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“…Part of the variability of response between dogs is due to the finding that in six animals (nos. 5, [8][9][10][11][12] hepatic vein insulin levels were lower than the simultaneous arterial levels, a situation which is not tenable during active insulin secretion. The glucose levels, however, were above arterial values, confirming that hepatic vein blood was indeed being sampled.…”

Section: Methodsmentioning

confidence: 88%

“…The glucose levels, however, were above arterial values, confirming that hepatic vein blood was indeed being sampled. This problem has been encountered by other investigators (8,10,17) and is probably due to large differences in insulin concentration in the various hepatic veins consequent upon differential distribution of pancreatic venous blood within the major branches of the portal vein, as demonstrated by Kanazawa et al (10). The effect of a spuriously low hepatic vein insulin concentration would be to falsely elevate hepatic insulin extraction or clearance, and it is possible that the augmented insulin extraction seen after glucose administration in dogs no.…”

Section: Methodsmentioning

confidence: 92%

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Effect of Intraduodenal Glucose Administration on Hepatic Extraction of Insulin in the Anesthetized Dog

Kaden¹,

Harding²,

Field³

1973

J. Clin. Invest.

137

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A B S T R A C T Extraction of insulin by the liver after administration of glucose in the duodenum has been studied in fourteen anesthetized dogs. Plasma insulin and glucose were measured in the portal vein hepatic vein and hepatic artery. During the control period 40 ±3% of the approximately 11 mU of insulin presented to the liver/min was removed during a single transhepatic passage. Within 5 min after glucose administration, the amount of insulin reaching the liver increased significantly. In some animals this increase preceded any significant increase in the glucose concentration of the femoral artery. After glucose administration, hepatic extraction of insulin remained unchanged in five animals and rose significantly in nine. In five of the latter animals, the increase may have been more apparent than real due to nonrepresentative sampling of hepatic venous blood. However, for the whole group of animals, comparison of arterial insulin levels with the amount of insulin delivered to the liver suggested a transient increase in insulin extraction between 5 and 50 min after glucose administration. In no animal was there a decrease in the proportion of insulin extracted by the liver after glucose administration. The results indicate that the extraction process is not saturable at physiological insulin levels. Prior to glucose administration, net hepatic glucose output averaged between 30 and 40 mg/min. After glucose administration, the liver began to take up glucose and there was a significant correlation between hepatic glucose uptake and the amount of insulin reaching the liver. However, since the amount of glucose presented to the liver also increased, it is not established that the insulin was responsible for the change in hepatic carbohydrate metabolism.The data demonstrate an increase in the absolute amount of insulin extracted by the liver after glucose administration and an important role for the liver in regulating peripheral insulin concentrations.

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Section: Methodsmentioning

confidence: 88%

Section: Methodsmentioning

confidence: 92%

Effect of Intraduodenal Glucose Administration on Hepatic Extraction of Insulin in the Anesthetized Dog

Kaden¹,

Harding²,

Field³

1973

J. Clin. Invest.

137

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“…7). DISCUSSION The liver has long been considered the most important organ for removal of insulin from the circulation (30)(31)(32). Since all endogenously secreted insulin must pass through the liver before reaching peripheral tissues, the degree of hepatic extraction of insulin can markedly influence systemic insulin levels (31,32).…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, there is general agreement that a substantial amount of portal vein insulin is taken up by the liver in a single transhepatic passage. Kaplan and Madison (33) estimated that 54% of insulin injected intraportally was extracted by the liver during a single passage, while Samols and Ryder (30) found that the mean hepatic insulin retention in the fasting state was 41%. As yet similar studies with proinsulin have not been published, but it is obvious that posthepatic blood levels and ratios of insulin and proinsulin will be markedly affected by the relative handling of the two polypeptides by the liver.…”

Section: Resultsmentioning

confidence: 99%

The Metabolism of Proinsulin and Insulin by the Liver

Rubenstein¹,

Pottenger²,

Mako³

et al. 1972

J. Clin. Invest.

159

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A B S T R A C T The removal of bovine proinsulin by the isolated perfused rat liver has been studied and the results compared with the removal of insulin. At high concentrations of insulin (> 180 ng/ml) the removal process was saturated and the ti varied between 35 and 56 min. With low initial insulin levels the disappearance followed first-order kinetics, the mean regression coefficient being -0.022, to 13.8 min, and the hepatic extraction 4.0 ml/min. The results with proinsulin were in striking contrast to these findings. At both high and low concentrations the hepatic removal of proinsulin was considerably slower, averaging 10-15 times less than that of insulin. Specific immunoassay techniques and gel filtration of samples taken from perfusions to which both labeled and unlabeled proinsulin had been added did not show conversion to either insulin or the C-peptide.Bovine and rat 'I-labeled proinsulins were degraded more slowly than bovine insulin-'1I by bovine and rat liver homogenates. Both proinsulin and insulin inhibited the degradation of insulin-tI, equimolar quantities of proinsulin being 2-5 times less effective than insulin.These results indicate significant differences in the capacity of the liver to remove and degrade insulin and proinsulin. The low hepatic extraction of proinsulin may account for its prolonged half-life in vivo and contribute to its relatively high plasma concentration in the fasting state. Furthermore this finding will have to be taken into account in the interpretation of changes in the proinsulin: insulin ratios in peripheral blood in a variety of metabolic situations.

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“…activity to porcine and human insulin (Sando et al, 1970;Berson & Yalow, 1959;Grodsky, 1965;Falkmar & Whson, 1967;Samols & Ryder, 1961;Yalow & Berson, 1964) Thus, it is expected that circulating bonito insulin can be immunologically distinguished from endogenous insulin when administered to man.…”

mentioning

confidence: 99%

Effect of Prior Infusion of Exogenous Bonito Insulin on Glucose-Induced Insulin Release in Man

1973

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SynopsisIn order to investigate a possible short feedback mechanism of insulin secretion, the effect of prior infusion of bonito insulin upon glucose-induced insulin secretion in man was studied. The increase in plasma insulin after intravenous injection of a glucose solution was analysed under prior sustaining infusion of bonito insulin at the concentration of 12mU/0.5ml/min and 6mU/0.5ml/min.These concentrations of bonito insulin were shown to have had no effect on the blood sugar levels, nor on the basal insulin levels. After the prior eight hour infusion of exogenous insulin, the increase in glucoseinduced insulin secretion was significantly smaller than that produced after infusion of saline as a control. The magnitude of the inhibition in plasma insulin elevation was more remarkable at the higher dose of insulin. The level of blood sugar after glucose injection shown no significant change.The half-life of immunoreactive insulin in plasma was determined after prior infusion of bonito insulin or saline for three hours. There was not tendency to any difference in T 1/2 between saline treated subjects and subjects who had received the rapid injection of porcine insulin prior to the infusion of bonito insulin.

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Studies on Tissue Uptake of Insulin in Man Using a Differential Immunoassay for Endogenous and Exogenous Insulin*

Cited by 136 publications

References 21 publications

Effect of Intraduodenal Glucose Administration on Hepatic Extraction of Insulin in the Anesthetized Dog

Effect of Intraduodenal Glucose Administration on Hepatic Extraction of Insulin in the Anesthetized Dog

The Metabolism of Proinsulin and Insulin by the Liver

Effect of Prior Infusion of Exogenous Bonito Insulin on Glucose-Induced Insulin Release in Man

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