Coculture of primary rat hepatocytes and nonparenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro.

Villafuerte, Betty C.; Koop, B L; Pao, Ching-I; Gu, Luming; Birdsong, George G.; Phillips, L S

doi:10.1210/endo.134.5.7512496

Cited by 65 publications

(45 citation statements)

References 6 publications

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“…Plasma IGFBP-3 levels are primarily influenced by GH and nutritional status: GH stimulates hepatic synthesis of IGFBP-3, probably indirectly through IGF-I (Villafuerte et al 1994), and fasting or malnutrition causes a decrease in circulating IGFBP-3 (Clemmons & Underwood 1991). In fish, candidates for IGFBP-3 have been detected based on molecular size and responses to GH injection and fasting on Western ligand blotting (Kelley et al 1992, Siharath et al 1995, Shimizu et al 1999, Park et al 2000.…”

Section: Figurementioning

confidence: 99%

Development of an RIA for salmon 41 kDa IGF-binding protein

Shimizu¹,

Hara²,

Dickhoff³

2003

Journal of Endocrinology

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Salmon plasma contains at least three IGF-binding proteins (IGFBPs) with molecular masses of 41, 28 and 22 kDa. The 41 kDa IGFBP is similar to mammalian IGFBP-3 in size, type of glycosylation and physiological responses. In this study, we developed an RIA for the 41 kDa IGFBP. The 41 kDa IGFBP purified from serum was used for antibody production and as an assay standard. Binding of three different preparations of tracer were examined: 125 I-41 kDa IGFBP, I-IGF-I was not affected by added IGFs, and therefore it was chosen for the tracer in the RIA. Plasma 41 kDa IGFBP levels measured by RIA were increased by GH treatment (178·9 4·9 ng/ml) and decreased after fasting (95·0 7·0 ng/ml). The molarities of plasma 41 kDa IGFBP and total IGF-I were comparable, and they were positively correlated, suggesting that salmon 41 kDa IGFBP is a main carrier of circulating IGF-I in salmon, as is mammalian IGFBP-3 in mammals. During the parr-smolt transformation (smoltification) of coho salmon, plasma 41 kDa IGFBP levels showed a transient peak (182·5 10·3 ng/ml) in March and stayed relatively constant thereafter, whereas IGF-I showed peak levels in March and April. Differences in the molar ratio between 41 kDa IGFBP and IGF-I possibly influence availability of IGF-I in the circulation during smoltification.

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Section: Figurementioning

confidence: 99%

Development of an RIA for salmon 41 kDa IGF-binding protein

Shimizu¹,

Hara²,

Dickhoff³

2003

Journal of Endocrinology

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“…All three components of the 150 kDa complex are produced by distinct hepatic cell types and, specifically, hepatocytes synthesize the IGF peptide and the acidlabile subunit (ALS), while Kupffer and sinusoidal endothelial cells produce IGFBP-3 (10)(11)(12). Regarding the regulation of the synthesis of the 150 kDa complex subunits, it has been established that, besides GH and nutrients (13), several other factors, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…epidermal growth factor (EGF) (14), fibroblast growth factor and platelet-derived growth factor can modulate IGF-I production in liver (14) and in other target cells (15), where the IGF peptide can act through autocrine and paracrine mechanisms. In addition, the synthesis of IGFBP-3, the binding subunit of the complex, can be regulated by several factors in liver (12) and in other cell types (16). Clinical data obtained in hypopituitary subjects (17) or in subjects treated with GH, alone or in combination with IGF-I (18,19), demonstrate that ALS is primarily under the control of GH.…”

Section: Introductionmentioning

confidence: 99%

Effect of the somatostatin analog, octreotide, and of other hormones on the release of the acid-labile subunit of the 150 kDa complex by rat hepatocyte in primary culture

Barreca

Voci

Lee

et al. 1997

European Journal of Endocrinology

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Objective: In normal subjects, the major form of circulating IGF is the GH-dependent 150 kDa complex. The liver appears to be the main source of the three components of the 150 kDa complex and, in particular, hepatocytes synthesize the insulin-like growth factor (IGF) peptide and the acid-labile subunit (ALS), whereas Kupffer and sinusoidal endothelial cells produce IGF-binding protein-3 (IGFBP-3). We have studied the effects of the somatostatin analog octreotide, IGF-II, des(1-3)IGF-I, transforming growth factor (TGF)-b1 and tri-iodothyronine (T3) on ALS secretion into the medium conditioned by rat hepatocytes in primary culture. Methods: The regulation of ALS release was evaluated in the conditioned medium of adult rat hepatocytes exposed to increasing concentrations of test substances or to vehicle alone (control), after gel filtration in basic conditions, by immunoblot using an antiserum generated against the N-terminal 34 amino acids of human ALS.Results: The results demonstrate that: 1) octreotide in vitro produces a dose-dependent inhibition of both basal and GH-stimulated ALS secretion into the hepatocyte conditioned medium; 2) the release of ALS by adult rat hepatocytes is not affected by the presence during the incubation of des(1-3)IGF-I or IGF-II; 3) an inhibitory effect, although only with very high doses, can be observed after treatment with TGF-b1; and 4) a small but significant increase of ALS released into the medium can be seen when hepatocytes are treated with T3. Conclusions: Evaluation of the effect of substances known to affect the production of IGF peptides, the IGFBPs, or both, on adult rat hepatocytes in primary culture revealed no powerful stimulator, but instead a potent inhibitor of ALS release/synthesis. Our data suggest that the effect of somatostatin on the 150 kDa complex is mediated not only by the reduction in GH concentration, but also by a direct inhibition of ALS release or synthesis.

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“…Several studies have indicated that these proteins are produced in different hepatic cell populations. Rat hepatocytes have been shown to secrete IGFBP-1, IGFBP-2, and IGFBP-4 (Bö ni-Schnetzler et al, 1990;Menuelle et al, 1995;Villafuerte et al, 1991), whereas IGFBP-3 expression was only found in Kupffer cells, endothelial cells, and hepatic stellate cells (Scharf et al, 1995(Scharf et al, , 1996(Scharf et al, , 1998aVillafuerte et al, 1994Villafuerte et al, , 1995. IGF-I is mainly released from hepatocytes (Kachra et al, 1991;Scharf et al, 1998a;Scott et al, 1985aScott et al, , 1985b.…”

mentioning

confidence: 99%

Analysis of the IGF Axis in Preneoplastic Hepatic Foci and Hepatocellular Neoplasms Developing after Low-Number Pancreatic Islet Transplantation into the Livers of Streptozotocin Diabetic Rats

Scharf¹,

Ramadori²,

Dombrowski

2000

Laboratory Investigation

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SUMMARY:Preneoplastic hepatic foci have been demonstrated in liver acini, which drain the blood from intraportally transplanted pancreatic islets in streptozotocin-induced diabetic rats with mild persisting diabetes. In long-term studies of this animal model, hepatocellular adenomas and carcinomas (HCC) developed after a sequence of characteristic preneoplastic hepatic foci. In this experimental model, the local hyperinsulinism is thought to have a causative role. Because insulin and the insulin-like growth factor (IGF) axis are closely linked, an altered gene expression of the IGF axis components is likely. Therefore, preneoplastic hepatic foci and HCC were studied for the expression of IGF axis components. Glycogen-storing "early" preneoplastic hepatic foci were detectable several days after pancreatic islet transplantation. Northern blot analysis, in-situ hybridization, and immunohistochemical studies of these "early" lesions demonstrated increased expressions of IGF-I and IGF binding protein-4 (IGFBP-4) in altered parenchymal cells, and a decreased expression of IGFBP-1. IGF-II was not detected in these preneoplastic foci. HCC arising in this model had decreased expressions of IGF-I and IGFBP-4 but IGFBP-1 expression was not significantly altered. Some HCC showed a more than 100-fold overexpression of IGF-II, whereas other tumors were completely negative for IGF-II expression. Low IGF-I receptor expression was detected in preneoplastic foci and adjacent nonaltered liver tissue. However, HCC tissue consistently showed an increased IGF-I receptor expression, rendering these tissues susceptible to the mitogenic effects of IGF. The altered gene expression in glycogen-storing preneoplastic hepatic foci, especially the up-regulation of IGF-I and IGFBP-4 with the down-regulation of IGFBP-1, resemble the insulin-dependent regulation of these components in normal rat hepatocytes. These data agree with previous studies demonstrating a correspondence of the focal character, morphology, and enzyme pattern of preneoplastic hepatic foci with insulin effects on hepatocytes. The development from preneoplastic foci to HCC may be driven by insulin itself and/or an altered IGF axis component or yet unidentified factors. (Lab Invest 2000, 80:1399-1411.

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Coculture of primary rat hepatocytes and nonparenchymal cells permits expression of insulin-like growth factor binding protein-3 in vitro.

Cited by 65 publications

References 6 publications

Development of an RIA for salmon 41 kDa IGF-binding protein

Development of an RIA for salmon 41 kDa IGF-binding protein

Effect of the somatostatin analog, octreotide, and of other hormones on the release of the acid-labile subunit of the 150 kDa complex by rat hepatocyte in primary culture

Analysis of the IGF Axis in Preneoplastic Hepatic Foci and Hepatocellular Neoplasms Developing after Low-Number Pancreatic Islet Transplantation into the Livers of Streptozotocin Diabetic Rats

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