Fate of Rat Insulin in Rat-Liver Perfusion Studied by Adipose-Tissue Assay

Bürgi, H; Schwarz, K.; Kopetz, K.; Froesch, E. R.

doi:10.1016/s0140-6736(63)92987-8

Cited by 94 publications

(11 citation statements)

References 12 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: 89%

“…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. In recent studies with this system, Marshall, Gingerrich, and Wright (35) have monitored the hepatic extraction of porcine insulin by a sensitive and specific immunoassay.…”

Section: Resultsmentioning

confidence: 91%

“…were calculated according to Mortimore et al (16), and Burgi, Kopetz, Schwarz, and Froesch (19) C1 and C2 = initial and final concentrations over the time interval At, and Ca = asymptote approached by C after prolonged perfusion. Preliminary experiments with low concentrations of the two hormones indicated their disappearance from the medium (< 0.5 ng/ml) after prolonged perfusion (3-4 hr) and thus Ca was taken as zero.…”

Section: Introductionmentioning

confidence: 99%

“…Preliminary experiments with low concentrations of the two hormones indicated their disappearance from the medium (< 0.5 ng/ml) after prolonged perfusion (3-4 hr) and thus Ca was taken as zero. Using this value, the half-life was determined in the following equation: ti = log 2 X 2.3 X V/k (19).…”

Section: Introductionmentioning

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: 89%

Section: Resultsmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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

“…Compatible with our findings are reports that clearance of proinsulin by cyclically perfused liver is immeasurably small (4, 5). However, in general, it is difficult to compare our findings with those based on cyclic liver perfusions since, in many of these experiments, measurement of insulin uptake was begun at 5-6 min after the addition of insulin to the perfusate and since the parameters measured differ in important respects from those that we studied (4,5,40,59,60).…”

Section: Discussionmentioning

confidence: 84%