Decreased expression of liver epidermal growth factor receptors in rats with alloxan and streptozotocin diabetes

Lev-Ran, Arye; Hwang, David; Barseghian, Gegham

doi:10.1016/0006-291x(86)91204-0

Cited by 16 publications

(4 citation statements)

References 15 publications

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“…In this study we demonstrated a decrease in the number of EGF-binding sites on he¬ patic membranes from these two kinds of diabetic mice. Our data are consistent with the previous find¬ ings that EGF binding in the liver was reduced in alloxan-induced (Lev-Ran et al 1986) and streptozo¬ tocin-induced (Lev-Ran et al 1986;Kashimata et al 1987;Okamoto et al 1988) diabetic rats. Since the decrease in EGF binding was observed in both the genetically and streptozotocin-induced diabetic mice, the results are consistent with the view that such abnormalities are not due to the toxic effects of the diabetogenic agent on the liver or to obesity, but represent a general phenomenon in the diabetic state.…”

Section: Discussionsupporting

confidence: 96%

“…Previous studies have shown that binding of EGF to the receptor in rat hepatocytes is influenced by a number of factors including thyroid hormones (Mukku, 1984), age (Kashimata, Hiramitsu & Minami, 1988), sex (Kashimata et al 1988), fasting state (Freidenberg, Klein, Kladde et al 1986), liver re¬ generation (Earp & O'Keefe, 1981) and experimen¬ tal diabetes (Lev-Ran, Hwang & Barseghian, 1986;Kashimata, Hiramitsu & Minami, 1987;Okamoto, Kahn, Marón & White, 1988). However, it is not known whether the changes in the receptor level occur as a result of alterations in transcription of the EGF receptor gene or stability and/or translation of EGF receptor messenger RNA, or of the post-translational modification or translocation of the receptor itself.…”

Section: Introductionmentioning

confidence: 95%

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Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice

Kasayama

Yoshimura²,

Oka³

1989

Journal of Molecular Endocrinology

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The expression of hepatic epidermal growth factor (EGF) receptor gene was studied in genetically diabetic (C57BL/KsJ db/db) mice and streptozotocin-induced diabetic mice. The binding of 125I-labelled EGF to hepatic membrane preparations of genetically diabetic mice was only 35% of that of non-diabetic mice. Levels of EGF receptor messenger RNAs (10 and 6 kb) in the liver of the diabetic animals were also reduced by about 75%. In streptozotocin-induced diabetic mice, levels of hepatic EGF binding and messenger RNAs for EGF receptor were decreased to 27 and 30% of control levels respectively, at 5 weeks after injection of the drug. There were, however, no significant differences in levels of messenger RNAs for the structural protein beta-actin in the liver. In addition, levels of EGF receptor messenger RNAs in the kidney were similar between control and the two kinds of diabetic mice. Daily administration of insulin to the streptozotocin-induced diabetic mice increased the hepatic levels of EGF receptor messenger RNAs to almost normal levels. These results indicate that EGF binding to its receptor decreases in the liver of diabetic mice, involving alterations in the level of EGF receptor messenger RNAs, and that insulin is important for the regulation of EGF receptor gene expression in the liver but not in the kidney.

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Section: Discussionsupporting

confidence: 96%

Section: Introductionmentioning

confidence: 95%

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice

Kasayama

Yoshimura²,

Oka³

1989

Journal of Molecular Endocrinology

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“…In fact, our finding of the enhanced degradation of EGFR in Db cells seems to be one example. Several studies have also shown that the number of surface EGFR molecules is decreased in hepatocytes isolated from the streptozotocin-induced diabetes rat model [51]–[54]. If the enhanced degradation of EGFR occurs under diabetic conditions in hepatocytes, this could explain the decrease in the EGFR receptor at the cell surface in such cells.…”

Section: Discussionmentioning

confidence: 99%

A Resealed-Cell System for Analyzing Pathogenic Intracellular Events: Perturbation of Endocytic Pathways under Diabetic Conditions

et al. 2012

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Cell-based assay systems that can serve as cellular models of aberrant function in pathogenic organs would be novel and useful tools for screening drugs and clarifying the molecular mechanisms of various diseases. We constructed model cells that replicated the conditions in diabetic hepatocytes by using the cell resealing technique, which enables the exchange of cytosol. The plasma membrane of HeLa cells was permeabilized with the streptococcal toxin streptolysin O, and cytosol that had been prepared from wild-type or db/db diabetic mice was introduced into the resulting semi-intact cells. By resealing the plasma membrane by exposure to Ca2+, we created WT or Db model cells, in which the cytosolic conditions replicated those of healthy or diabetic liver. Interestingly, phosphorylation of p38 MAPK was promoted, whereas the level of endosomal phosphatidylinositol-3-phosphate was decreased, in Db cells. We investigated several endocytic pathways in WT and Db cells, and found that retrograde endosome-to-Golgi transport was delayed in a p38 MAPK-dependent manner in Db cells. Furthermore, the degradation pathway of the EGF receptor from endosomes to lysosomes was enhanced in Db cells, and this did not depend on the activation of p38 MAPK. The disease model cell system should become a powerful tool for the detection of aberrant processes in cells under pathogenic conditions and for therapeutic applications.

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“…These modulators include EGF itself, which causes down-regulation of its receptor (Aharonov, Pruss & Herschman, 1978;Das & Fox, 1978), cell density (Holley, Armour, Baldwin et al 1977; Pratt & Pastan, 1978), transformation (Todaro, DeLarco & Cohen, 1976;Hollenberg, Barret, Ts'o & Berhanu, 1979), glucocorticoids (Barker, Barsh, Carney & Cunningham, 1978), platelet-derived growth factor (Wrann, Fox & Ross, 1980), fibroblast growth factor (Fox, Wrann, Linsley & Vale, 1979) and transforming growth factor-ß (Assoian, 1985). In addition, exper¬ iments conducted in vivo have shown that hepatic EGF receptors are affected by thyroid hormones (Hayden & Severson, 1983;Mukku, 1984), fasting (Freidenberg, Klein, Kladde et al 1986) and experimental diabetes (Lev-Ran, Hwang & Barseghian, 1986;Kashimata, Hiramatsu & Minami, 1987).…”

Section: Introductionmentioning

confidence: 97%

Differential secretory rhythm of growth hormone controls the number of hepatic epidermal growth factor receptors in the rat

Kashimata¹,

Hiramatsu²,

Minami³

1989

Journal of Endocrinology

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The effect of human GH (hGH) on hepatic epidermal growth factor (EGF) receptors in the rat was investigated. Continuous administration of hGH through an osmotic minipump, mimicking the female pattern of GH secretion, to normal male rats reduced the binding of 125I-labelled EGF to hepatic membranes to the normal female levels. The same treatment of hGH applied to hypophysectomized males had no apparent effect on EGF binding. Intermittent s.c. administration of hGH twice a day (every 12 h), mimicking the male pattern of GH secretion, to hypophysectomized male and/or normal female rats, caused a significant increase in EGF binding to the levels of normal male rats. Scatchard analysis of the binding data clearly showed that the change in EGF binding was due to a change in the number of EGF receptors. The results on the affinity labelling and phosphorylation of EGF receptors were in good agreement with those showing differences in the number of EGF receptors among the experimental groups. These results indicate that the number of hepatic EGF receptors in the rat is regulated by the differential secretory rhythm of pituitary GH between the sexes.

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Decreased expression of liver epidermal growth factor receptors in rats with alloxan and streptozotocin diabetes

Cited by 16 publications

References 15 publications

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice

Decreased expression of hepatic epidermal growth factor receptor gene in diabetic mice

A Resealed-Cell System for Analyzing Pathogenic Intracellular Events: Perturbation of Endocytic Pathways under Diabetic Conditions

Differential secretory rhythm of growth hormone controls the number of hepatic epidermal growth factor receptors in the rat

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