Effect of adrenalectomy and glucocorticoid treatment on the levels of an insulin-sensitive glycosyl-phosphatidylinositol in isolated rat hepatocytes

Cabello, M. Angeles; Sánchez‐Arias, Juan A.; Liras, Antonio; Mato, JoséM.; Feliu, Jaume Cruz i

doi:10.1016/0303-7207(90)90173-6

Cited by 10 publications

(15 citation statements)

References 17 publications

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“…A similar impairment in the glycosyl-PtdIns ' signalling system has also been demonstrated in hepatocytes isolated from rats with dexamethasone-induced insulin resistance [ 17,231 or with streptozotocin-induced diabetes [39]. Furthermore, Juhl and Flyvbjerg [40] have reported a marked decrease in the rate of glycosyl-PtdIns biosynthesis in adipocyte membranes isolated from streptozotocin-diabetic rats when compared with that measured in adipocyte membranes isolated from normal animals.…”

Section: Aging and Glycosyl-ptdins Signalling System In Isolated Rat supporting

confidence: 53%

“…Moreover, Macaulay and coworkers have demonstrated an impairment of the insulinstimulated breakdown of glycosyl-F'tdIns in adipocytes isolated either from streptozotocin-diabetic rats [41] or from patients with type-I1 diabetes [42]. The fact that different states of insulin resistance, like glucocorticoid treatment [17], streptozotocin-induced diabetes [39] or aging, may cause similar changes in the glycosyl-PtdIns-dependent signalling system suggest that these modifications could be the common consequence of an altered insulin action at the cellular level and possibly not the primary defect.…”

Section: Aging and Glycosyl-ptdins Signalling System In Isolated Rat mentioning

confidence: 99%

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Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Sánchez‐Arias

Sánchez-Gutiérrez

Guadaño³

et al. 1993

European Journal of Biochemistry

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An inositol-phosphate glycan (InsP glycan), which is the polar head group of an insulin-sensitive glycosyl-phosphatidylinositol (glycosyl-PtdIns), has been reported to mimic some insulin actions when added to different types of cells. In connection with this, a specific, time-dependent and energy-dependent transport system for this InsP glycan has been identified in isolated rat hepatocytes [Alvarez, J. F., Shchez-Arias, J. A., Guadaiio, A., Estevez, F., Varela, I., Feliu, J. E. & Mato, J. M. (1991) Biochem. J. 274,369-3741. Here we have investigated the glycosyl-PtdIns-dependent insulin-signalling system in hepatocytes isolated from either 3-month-old or 24-month-old rats. Aging reduced the stimulatory effect of insulin on [U-'4C]glucose incorporation into glycogen, caused a significant decrease in basal glycosyl-PtdIns levels and blocked the insulin-mediated hydrolysis of this lipid. In 24-month-old rats, we also observed a diminution in the rate of hepatocyte InsP-glycan uptake and a marked reduction of the stimulatory effect of this compound on glycogen synthesis. These results support the hypothesis that insulin resistance associated with aging is accompanied by an impairment of the glycosyl-PtdIns-dependent cellular signalling system.In recent years, reports from different laboratories have supported the involvement of a phospholipase-C-catalyzed hydrolysis of a glycosyl-phosphatidylinositol (glycosylPtdIns) in the mechanism of insulin action (for reviews see [l-31). The polar head group generated by the hydrolysis of glycosyl-PtdIns is an inositol-phosphate glycan (InsP glycan), which seems to contain a hexosamine-inositol-phosphate moiety and several additional sugars [4-71. This InsP glycan has been reported to simulate the effects of insulin on the activity of certain insulin-modulated enzymes in cell-free systems [8-101. In intact cells, InsP glycan also mimics some of the metabolic actions of insulin on lipid and glucose metabolism, cyclic-AMP levels, amino-acid uptake, pattern of phosphorylatioddephosphorylation of proteins and mRNA expression [ 11 -181.It is well established that insulin promotes the release of InsP glycan to the extracellular medium [19, 201. In fact, the majority (approximately 80%) of insulin-sensitive glycosylPtdIns in rat hepatocytes has been localized at the outer cell surface [21]. Moreover, addition of anti-(InsP glycan) immunoglobulins to cultured BC3H1 myocytes selectively blocked insulin-induced activation of pyruvate dehydrogenase and provoked the accumulation of insulin-mediator activity in the extracellular medium [22].As a possible connection between the extracellular release of InsP glycan and its intracellular effects, we have recently identified a specific, time-dependent and energy-dependent InsP-glycan-transport system for this compound in isolated rat hepatocytes, which is antagonized by micromolar Although experimental evidence supporting the implication of glycosylated forms of PtdIns in the signal-transduction mechanism of insulin is increasingly strong, li...

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Section: Aging and Glycosyl-ptdins Signalling System In Isolated Rat supporting

confidence: 53%

Section: Aging and Glycosyl-ptdins Signalling System In Isolated Rat mentioning

confidence: 99%

Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Sánchez‐Arias

Sánchez-Gutiérrez

Guadaño³

et al. 1993

European Journal of Biochemistry

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“…Mangiapane et al, have shown decrease in the triglyceride and PC content of the cultures of rat hepatocytes with Dex pre-incubation [60]. Other researchers have shown decreased glycosylated PC levels in hepatocyte [53]. All of the above reports either indicate or directly state the involvement of Dex in lipid metabolism.…”

Section: Discussionmentioning

confidence: 85%

“…In this study, the authors used fifty times higher dose of Dex. The regulatory role of glucocorticoids in gluconeogenic and insulin resistance during development has known [52,53]. In hepatocytes, the effect of induction of gluconeogenesis after Dex treatment was shown [54].…”

Section: Discussionmentioning

confidence: 99%

Dexamethasone treatment alters kinetics properties of liver mitochondrial F<sub>0</sub>.F<sub>1</sub>-ATPase and membrane lipid profiles in developing and adult rats

Pandya¹,

Agarwal²,

Modi³

et al. 2013

AER

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Dexamethasone-a potent synthetic glucocorticoid-has multiple diagnostic and therapeutic applications in wide range of age groups. However, the side-effects of dexamethasone (Dex) treatment including those on development are becoming increasingly apparent. Since the developmental processes are energy-dependent, we examined the effects of chronic Dex treatment on kinetics properties of liver mitochondrial F 0 .F 1 -ATPase and mitochondrial membrane lipid profiles in rats belonging to different developmental age groups (2, 3, 4 and 5 weeks) and in adults (~8 weeks). The animals were treated with a subcutaneous dose of 2 mg of Dex/kg body weight (or saline as vehicle) for three alternative days (at around 7.00 A.M.) prior to the day of sacrifice. Dex treatment resulted in significant reduction in F 0 .F 1 -ATPase activity in developmental age groups and in adults as compared to their age-matched vehicle-treated control group. The substrate kinetics analysis of F 0 .F 1 -ATPase resolved Km and Vmax values in 3 components in all the control age groups; whereas Dex treatment significantly altered the Km and Vmax values or abolished the entire components in age-specific manner. Dex treatment significantly lowered the energy of activation and altered phase transition temperature (Tt˚C) in all the developmental age groups and in adults. Dex treatment significantly increased the contents of total phospholipid (TPL), individual phospholipids classes and cholesterol (CHL) in all the developmental age groups whereas opposite pattern was observed in adults. The mitochondrial membrane became more fluidized in the developing age groups (2, 4 and 5 weeks); whereas no change was observed in 3-week and adult groups following Dex treatment. In present study, our data demonstrate comprehensive deleterious effects of chronic Dex treatment on liver mitochondrial membrane structure and F 0 .F 1 -ATPase functional properties with respect to energy metabolism. At the same time, our data also warns against excessive repeated use of antenatal DEX in treatments in growing and adult human patients.

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“…Similarly, a correlation between the levels of GPI and the induction of insulin receptors has been described in T-cells (14) and in CHO cells bearing normal human insulin receptors, the GPI content is threefold higher than in parental cells and in cells bearing a mutant receptor lacking in tyrosine kinase activity (35). Also, dexamethasone administration to rats is accompanied by a marked decrease in the hepatocyte content of insulin receptors and of an insulin-sensitive GPI, whereas bilateral adrenalectomy provokes a significant increase in both parameters (37). These findings suggest that insulin may regulate not only the number of its own receptors but also the concentration of GPI, which may be of interest in the study of transduction of signals in insulin-resistant states.…”

Section: Discussionmentioning

confidence: 92%

Insulin Does Not Induce the Hydrolysis of a Glycosyl Phosphatidylinositol in Rat Fetal Hepatocytes

Ruiz-Albusac

Zueco²,

Velázquez³

et al. 1993

Diabetes

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An inositol phosphoglycan that is the polar head group of a glycosyl phosphatidylinositol has been considered as a putative mediator of insulin action. To gain insight into the functions of this hormone during development, the relationships between insulin, insulin receptors, glycosyl phosphatidylinositol, and inositol phosphoglycan were studied. Glycosyl phosphatidylinositol was isolated and characterized in fetal liver as early as day 15 of intrauterine life. In isolated hepatocytes from fetal and adult rats labeled with [3H]glucosamine, [3H]galactose, or [3H]myo-inositol, these molecules were incorporated into glycosyl phosphatidylinositol. In hepatocytes labeled with [3H]glucosamine and then allowed to react with [1-14C]IAI, the [3H]glycosyl phosphatidylinositol was purified as the 14C-labeled amidinated lipid. Glycosyl phosphatidylinositol molecules from fetal and adult cells were sensitive to hydrolysis by a phosphatidylinositol-specific phospholipase C from B. cereus. The product of this hydrolysis inhibits the activity of a cAMP-dependent protein kinase, whereas this effect was abolished by nitrous acid deamination. In isolated hepatocytes from adult animals, an inverse correlation between extracellular insulin and the number of insulin receptors and the cellular content of glycosyl phosphatidylinositol was observed. However, in fetal hepatocytes insulin failed to reduce the glycosyl-phosphatidylinositol content when labeled either with [1-14C]isethionyl acetimidate or [3H]glucosamine, whereas insulin-like growth factor I produced a significant hydrolysis of glycosyl phosphatidylinositol. Fetal and adult hepatocytes were incubated with insulin or inositol phosphoglycan after which glycogen phosphorylase activities were determined. Inositol phosphoglycan mimicked the action of insulin on both forms of the enzyme from adult hepatocytes, whereas in fetal cells insulin did not change, and purified inositol phosphoglycan reduced the activities of glycogen phosphorylase. These findings suggest a dissociation between insulin receptor occupancy and the expected hormonal effects in fetal hepatocytes. This could be related to alterations at a postreceptor level.

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Effect of adrenalectomy and glucocorticoid treatment on the levels of an insulin-sensitive glycosyl-phosphatidylinositol in isolated rat hepatocytes

Cited by 10 publications

References 17 publications

Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Dexamethasone treatment alters kinetics properties of liver mitochondrial F<sub>0</sub>.F<sub>1</sub>-ATPase and membrane lipid profiles in developing and adult rats

Insulin Does Not Induce the Hydrolysis of a Glycosyl Phosphatidylinositol in Rat Fetal Hepatocytes

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Effect of adrenalectomy and glucocorticoid treatment on the levels of an insulin-sensitive glycosyl-phosphatidylinositol in isolated rat hepatocytes

Cited by 10 publications

References 17 publications

Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Changes in the insulin‐sensitive glycosyl‐phosphatidyl‐inositol signalling system with aging in rat hepatocytes

Dexamethasone treatment alters kinetics properties of liver mitochondrial F&lt;sub&gt;0&lt;/sub&gt;.F&lt;sub&gt;1&lt;/sub&gt;-ATPase and membrane lipid profiles in developing and adult rats

Insulin Does Not Induce the Hydrolysis of a Glycosyl Phosphatidylinositol in Rat Fetal Hepatocytes

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Dexamethasone treatment alters kinetics properties of liver mitochondrial F<sub>0</sub>.F<sub>1</sub>-ATPase and membrane lipid profiles in developing and adult rats