Removal of insulin by perfused rat liver: Effect of concentration

Mondon, Carl E.; Olefsky, Jerrold M.; Dolkas, C. B.; Reaven, Gerald M.

doi:10.1016/0026-0495(75)90016-5

Cited by 79 publications

(44 citation statements)

References 11 publications

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“…The present experiments have considerably substantiated the existence of such a correlation between plasma insulin concentration and hepatic insulin removal, and have extended it to livers of both lean and obese-hyperglycemic (ob/ob) mice. This study indicates that in livers of both lean and obese-hyperglycemic mice, the removal of insulin increases as the concentration of the hormone in the portal vein increases, until the process eventually becomes saturated (Table II), as previously suggested for perfused livers of normal rats (9). Considerably lower insulin concentrations were required to reach saturation in livers from ob/ob than from normal mice (Table II).…”

Section: Resultssupporting

confidence: 77%

“…Several in vivo investigations carried out in man and dog indicate that this organ removes significant quantities of insulin (1)(2)(3)(4). This has been further substantiated in the rat by measurement of insulin removal in vitro by liver perfusion techniques (5)(6)(7)(8)(9). Such in vitro studies have suggested that the insulin removal was greater when less insulin reached the liver (10,11).…”

Section: Introductionmentioning

confidence: 90%

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An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice.

Karakash¹,

Assimacopoulos-Jeannet²,

Jeanrenaud³

1976

J. Clin. Invest.

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A B S T R A C T Obese-hyperglycemic (ob/ob) mice have the interesting feature of being hyperinsulinemic, thus having some characteristics in common with human maturity-onset diabetics. As the cause of hyperinsulinemia in these mice is not established, and as the liver is known to play a role in determining the amount of hormone that reaches the periphery, it was hypothesized that an anomaly in the hepatic handling of insulin might prevail in obese-hyperglycemic mice. Immunoreactive insulin was therefore measured in the perfusate before and after a single passage through perfused livers of lean and ob/ob mice, permitting the calculation of insulin removal. It was found that the removal of insulin by livers of lean mice increased with increasing concentrations of the hormone in the portal vein. The removal process had a limited capacity, however, and as a consequence the percentage of hormone removed by the liver actually decreased when portal insulin concentrations increased. Insulin removal by livers of ob/ob mice had qualitatively the same characteristics but was considerably less efficient than in normal livers. Due to this, more insulin was found in the perfusate leaving the liver of ob/ob mice than in that of controls, at any insulin concentration tested. These observations suggest that in obese-hyperglycemic mice more of the hormone may reach the periphery and thus contribute to hyperinsulinemia. The present study further suggests that the anomaly of insulin removal observed in perfused livers of ob/ob mice might be secondary to hyperinsulinemia, since it was partly corrected upon artificially decreasing the circulating levels of insulin (e.g. via a fast, anti-

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Section: Resultssupporting

confidence: 77%

Section: Introductionmentioning

confidence: 90%

An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice.

Karakash¹,

Assimacopoulos-Jeannet²,

Jeanrenaud³

1976

J. Clin. Invest.

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“…A large body of in vitro and in vivo (45)(46)(47)(48) work has confirmed the importance ofthis pathway and elucidated the kinetic and enzymatic characteristics of this function. Interposed between pancreatic insulin output and systemic circulation, the liver is exposed to higher insulin concentrations than any other organ.…”

Section: Resultsmentioning

confidence: 91%

Splanchnic insulin metabolism in obesity. Influence of body fat distribution.

Peiris¹,

Mueller²,

Smith³

et al. 1986

J. Clin. Invest.

324

143

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The effects of obesity and body fat distribution on splanchnic insulin metabolism and the relationship to peripheral insulin sensitivity were assessed in 6 nonobese and 16 obese premenopausal women.When compared with the nonobese women, obese women had significantly greater prehepatic production and portal vein levels of insulin both basally and following glucose stimulation. This increase correlated with the degree of adiposity but not with waist-to-hip girth ratio (WHR). WHR, however, correlated inversely with the hepatic extraction fraction and directly with the posthepatic delivery of insulin. The latter correlated with the degree of peripheral insulinemia. The decline in hepatic insulin extraction with increasing WHR also correlated with the accompanying diminution in peripheral insulin sensitivity.Increasing adiposity is thus associated with insulin hypersecretion. The pronounced hyperinsulinemia of upper body fat localization, however, is due to an additional defect in hepatic insulin extraction. This defect is closely allied with the decline in peripheral insulin sensitivity.

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“…Insulin secreted from the B-cell reaches the liver, where about 50% of insulin is extracted and modulated, according to Madison and Kaplan (1958), Kaden et al (1973) and Mondon et al (1975). In contrast, as far as C-peptide is concerned, only a small part is handled in the liver and most of C-peptide is excreted from the kidney (Katz and Rubenstein 1973;Sherwin et al 1976;Rabkin et al 1978).…”

Section: Discussionmentioning

confidence: 99%

Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man.

Sakai

Ohneda

Nihei

et al. 1982

Tohoku J. Exp. Med.

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In order to clarify the mechanism of insulin secretion, responses of insulin (IRI) and C-peptide (CPR) in plasma to various stimuli were investigated in normal subjects and patients with diabetes mellitus, liver cirrhosis, chronic nephritis or insulinoma. The response of plasma IRI and CPR to oral glucose load was less marked in the mild and moderate diabetes groups than in the normal controls. Neither IRI nor CPR in the severe diabetes group responded to oral glucose. The patients with liver cirrhosis revealed an exaggerated and delayed response of IRI and CPR, and a lowered CPR/IRI ratio, indicating a remarkable response of IRI to glucose. In contrast, the patients with chronic nephritis showed a prominent rise of CPR alone. In the insulinoma patients, both plasma IRI and CPR increased after glucose load. In the response to glucose, there was approximately 30-min lag time between the peaks of IRI and CPR in the normal controls and the patients with various diseases. Following arginine infusion, plasma IRI and CPR increased in the normal subjects and the patients with moderate diabetes. In the normal subjects, plasma IRI reached a peak at 6 min and 3 min in response to tolbutamide and glucagon, respectively, which elicit an abrupt and sharp rise of insulin from B-cells. However, diabetic patients showed a minimal change in plasma IRI and CPR, whereas there was an exaggerated response of plasma IRI and CPR in insulinoma patients. In analysis of responses of plasma IRI and CPR to tolbutamide or glucagon, there was a lag time longer than 10 min in the normal subjects.The present study confirms the concurrent release of C-peptide from the B-cells in the secretion of insulin. In addition, it was suggested that insulin and C-peptide are mainly handled in the liver and the kidney, respectively.Furthermore, a longer lag time between the peaks of IRI and CPR in response to tolbutamide or glucagon did not necessarily indicate a simultaneous release of insulin and C-peptide from the B-cell, but a delayed release of the latter.glucose tolerance test; arginine; tolbutamide; glucagon The development of the immunoassay for insulin has made the measurement of a minute amount of insulin in plasma possible and has given much information concerning B-cell function of the pancreas. In 1967, Steiner and his co-workers discovered proinsulin from insulinoma tissues as well as from the normal rat

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Removal of insulin by perfused rat liver: Effect of concentration

Cited by 79 publications

References 11 publications

An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice.

An anomaly of insulin removal in perfused livers of obese-hyperglycemic (ob/ob) mice.

Splanchnic insulin metabolism in obesity. Influence of body fat distribution.

Analysis of insulin secretion based on changes in plasma insulin and C-peptide in man.

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