The Interactions of Proinsulin with Insulin Receptors on the Plasma Membrane of the Liver

Freychet, P

doi:10.1172/jci107845

Cited by 71 publications

(59 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Proinsulin, which has 5-10% of the biologic activity of insulin (31), is removed by the isolated perfused rat liver 10-15 times less rapidly than insulin (7). These figures correlate with the known binding of proinsulin to hepatic insulin receptors, which is 5-10% of that for insulin (32). C-peptide, which exerts no biologic activity in the liver, is not metabolized by this organ (33,34).…”

Section: Discussionmentioning

confidence: 98%

Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Jaspan¹,

Polonsky²

1982

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T Oral glucose (25 g) fed to seven healthy, conscious dogs resulted in an increase in peripheral plasma glucose from 109±3 to 178±10 mg/dl. Concurrently serum insulin increased in the portal vein to levels approximately threefold greater than those in the periphery. Hepatic insulin delivery rose from 10.8±0.7 to 59.0±19.9 mU/min at 60 min, coincident with an increased hepatic insulin extraction from 3.3 to 41.4 mU/min (corresponding to an increase in hepatic extraction from 31±4 to 59±7%), both returning to basal at 3 h. In each animal there was a positive correlation between hepatic insulin delivery and extraction (r = 0.80, P < 0.001 for the seven experiments combined). These changes in hepatic insulin delivery and extraction after glucose feeding were correlated with changes in hepatic glucose metabolism associated with insulin action. As hepatic insulin extraction increased, hepatic glucose output declined, both parameters returning to basal levels by 3 h, indicating a negative correlation between hepatic insulin extraction and hepatic glucose output (r = 0.63, P < 0.001; n = 7).The factors that mediate this marked and rapidly occurring increase in hepatic insulin extraction after oral glucose are unknown, and may include hepatic insulin delivery, glucose levels in the blood supplying the liver, factors related to increased hepatic blood flow, and gut factors released by oral glucose intake. The association of changes in hepatic insulin extraction in vivo with an insulin effect on the liver as measured

show abstract

Section: Discussionmentioning

confidence: 98%

Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Jaspan¹,

Polonsky²

1982

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The work of Mortimore and Tietze with cyclically perfused rat livers suggested that insulin degradation required prior "capture" and transport to a presumed intracellular degrading site (3). Stoll et al (4) and Rubenstein,et al (5) have shown that proinsulin, which has relatively low biological potency (6,7) and which binds poorly to rat liver plasma membranes (8), is extracted very slowly by the isolated perfused liver. In addition, Csorba, et al (9) have shown that 'I-desalanyl-desasparaginyl insulin, an analogue with very low biological potency (10)(11)(12)(13)(14), which inhibits the binding of 'I-insulin to insulin receptors only at relatively high concentrations (10)(11)(12)(13)(14)(15), is removed more slowly from the plasma of dogs than 'I-insulin in a comparable dose.…”

Section: Introductionmentioning

confidence: 99%

Retention and degradation of 125I-insulin by perfused livers from diabetic rats.

Terris¹,

Steiner²

1976

J. Clin. Invest.

135

View full text Add to dashboard Cite

“…METHODS Materials. The rat and human insulins, 20 (28); monoiodinated insulin, 380 uCi/jsg (29); and monoiodinated-proinsulin, 250 /Ci/,g (30) were labeled by the chloramine-T method (31). L-[4,5-'H]leucine (40 Analytical grade anion-exchange resin (AGI-X2) was from Bio-Rad, (Paris).…”

Section: Introductionmentioning

confidence: 99%

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

García¹,

Jarrousse²,

Rosselin³

1976

J. Clin. Invest.

View full text Add to dashboard Cite

A B S T R A C T The purpose of the present study was to investigate the regulation of insulin biosynthesis during the perinatal period. The incorporation of [3H]leucine into total immunoreactive insulin (IRI) and into IRI fractions was measured by a specific immunoprecipitation procedure after incubation, extraction, and gel filtration in isolated 3-day-old rat pancreases without prior isolation of islets. IRI fractions were identified by their elution profile, their immunological properties, and their ability to compete with the binding of "I-insulin in rat liver plasma membranes. No specific incorporation of [3H]leucine was found in the IRI eluted in the void volume, making it unlikely that this fraction behaves as a precursor of (pro)insulin in this system. In all conditions tested, the incorporation of [8H]leucine was linearly correlated with time. Optimal concentration of glucose (11 mM cose and was not modified by any further increase in glucose concentrations up to 27.5 mM. Theophylline or dbcAMP at 10 mM concentration did not reverse the somatostatin inhibitory effect on either insulin biosynthesis or release. Somatostatin also inhibited both processes in isolated islets from the 3-day-old rat pancreas. High Ca"+ concentration in the incubation medium reversed the inhibitory effect of somatostatin on glucoseinduced insulin biosynthesis as well as release. In both systems the inhibitory effect of somatostatin on insulin biosynthesis and release correlated well. Glipizide (10-100 ,M) and tolbutamide (400 ELM) inhibited the stimulatory effect of glucose, dbcAMP, and theophylline on [8H]leucine incorporation into IRI. The concentrations of glipizide that were effective in inhibiting [3H]leucine incorporation into IRI were smaller than those required to inhibit the phosphodiesterase activity in isolated islets of 3-day-old rat pancreas.These data suggest the following conclusions: (a) the role of the cAMP-phosphodiesterase system on insulin biosynthesis is likely to be greater in newborns than in adults; (b) the greater effectiveness of glucose and the cAMP system on insulin biosynthesis than on insulin release might possibly be related to the rapid accumulation of pancreatic IRI which is observed in the perinatal period; (c) somatostatin, by direct interaction with the endocrine tissue, can inhibit glucose and cAMPinduced insulin biosynthesis as well as release; calcium reverses this inhibition; (d) sulfonylureas inhibit insulin biosynthesis in newborn rat pancreas an effect which has

show abstract

The Interactions of Proinsulin with Insulin Receptors on the Plasma Membrane of the Liver

Abstract: The interactions of proinsulin with the insulin-specific receptors were investigated in purified rat liver plasma membranes. These studies were de- (1) and the elucidation of its amino acid sequence (2) investigators have performed studies both

Cited by 71 publications

References 33 publications

Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Glucose ingestion in dogs alters the hepatic extraction of insulin. In vivo evidence for a relationship between biologic action and extraction of insulin.

Retention and degradation of 125I-insulin by perfused livers from diabetic rats.

Biosynthesis of proinsulin and insulin in newborn rat pancreas. Interaction of glucose, cyclic AMP, somatostatin, and sulfonylureas on the (3H) leucine incorporation into immunoreactive insulin.

Contact Info

Product

Resources

About