Metabolism of Insulin-I131 Studies in Isolated, Perfused Rat Liver and Hind-limb Preparations

Mortimore, Glenn E.; Tietze, Frank; Stetten, DeWitt

doi:10.2337/diab.8.4.307

Cited by 105 publications

(31 citation statements)

References 7 publications

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“…Nevertheless, the results obtained with initial insulin concentrations between 10 and 20 ng/ml (250-500 /U/ ml) (Table I), which is within the reported range for portal vein insulin levels in man (36), are almost identical with those of Buchanan, Solomon, Vance, Porter, and Williams (37) and Solomon et al (34). In addition, the rates for hepatic insulin extraction, which minimize methodological differences to a large extent, are similar to previously reported values (16,19,34,37). It is of interest that the rate of insulin removal slowed appreciably at perfusate concentrations greater than 80 ng/ml (2000 AU/ml) (Fig.…”

Section: Resultssupporting

confidence: 77%

“…Mortimore et al (16), using insulin-'I as a tracer, found that 40% of the insulin presented to the liver was removed in a single passage and that the hepatic extraction was approximately 3.0 ml/min. Solomon, Fenster, Ensinck, and Williams (34) obtained comparable results using an isolated fat cell bioassay to measure the disappearance of porcine insulin, while Burgi et al (19) found a hepatic clearance of 2.67 ml/min and half-disappearance time of 42 min for unlabeled rat insulin assayed by the rat epididymal fat pad method.…”

Section: Resultsmentioning

confidence: 99%

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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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Section: Resultssupporting

confidence: 77%

Section: Resultsmentioning

confidence: 99%

The Metabolism of Proinsulin and Insulin by the Liver

Rubenstein¹,

Pottenger²,

Mako³

et al. 1972

J. Clin. Invest.

159

View full text Add to dashboard Cite

show abstract

“…Mortimore, Tietze, and Stetten reported that the isolated perfused rat liver removed 40% of ["I] insulin (25 mU/ml) in a single passage (4). Insulin uptake was significantly less during perfusion of the hind limb.…”

Section: Introductionmentioning

confidence: 99%

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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“…and perfused in situ by a slight modification of the technique of Mortimore et al(1959). A Krebs-Ringer-Tris buffer (20 mM Tris-HCl, pH 7.4 oxygenated with 100% O2) was infused into the liver from the portal vein at a constant speed of 20 ml/min without recirculation by a peristaltic pump (Decarf-240, Taiyo Kagaku Co., Tokyo, Japan).…”

Section: Liver Perfusionmentioning

confidence: 99%