Isolation of a cDNA for the Catalytic Subunit of Rat Liver Glucose-6-Phosphatase: Regulation of Gene Expression in FAO Hepatoma Cells by Insulin, Dexamethasone and cAMP

Lange, Alex J.; Argaud, Doriane; el-Maghrabi, M R; Pan, Wansong; Maitra, Soumyajit; Pilkis, S J

doi:10.1006/bbrc.1994.1702

Cited by 119 publications

(73 citation statements)

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“…Cortisol and metabolic syndrome (29,30). Thus, as was expected, in this study, LHSD11B1 was found to be positively correlated with fasting glucose.…”

Section: European Journal Of Endocrinologysupporting

confidence: 87%

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Constantinopoulos

Michalaki

Κοττόρου

et al. 2015

European Journal of Endocrinology

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Context: Adrenal and extra-adrenal cortisol production may be involved in the development of metabolic syndrome (MetS). Objective: To investigate the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the expression of HSD11B1, nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptors) a (NR3C1a) and b (NR3C1b) in the liver, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) of severely obese patients with and without MetS. Methods: The study included 37 severely obese patients (BMI R40 kg/m 2 ), 19 with MetS (MetSC group) and 18 without (MetSK group), studied before and during bariatric surgery. Before the day of surgery, urinary free cortisol (UFC) and diurnal variation of serum and salivary cortisol were estimated. During surgery, biopsies of the liver, VAT and SAT were obtained. The expression of HSD11B1, NR3C1a and NR3C1b was evaluated by RT-PCR.Results: UFC and area under the curve for 24-h profiles of serum and salivary cortisol were lower in the MetSK group. In the MetSK group, mRNA levels of HSD11B1 in liver exhibited a negative correlation with liver NR3C1a (LNR3C1a) and VAT expression of HSD11B1 was lower than the MetSC group. Conclusions: We observed a downregulation of the NR3C1a expression and lower VAT mRNA levels of HSD11B1 in the MetSK group, indicating a lower selective tissue cortisol production and action that could protect these patients from the metabolic consequences of obesity. In the MetSK group, a lower activity of the HPA axis was also detected. Taken together, cortisol in tissue and systematic level might play a role in the development of MetS in severely obese patients.

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“…Cortisol and metabolic syndrome (29,30). Thus, as was expected, in this study, LHSD11B1 was found to be positively correlated with fasting glucose.…”

Section: European Journal Of Endocrinologysupporting

confidence: 87%

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Constantinopoulos

Michalaki

Κοττόρου

et al. 2015

European Journal of Endocrinology

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“…While the potential role of circulating lipids in regulating the expression of hepatic enzymes has generally been examined in vivo using dietary manipulations of fat intake (16), we believe that such an experimental approach may fail to address the direct role of circulating lipids on Glc-6-Pase mRNA and protein. In fact, the complex regulation of the hepatic expression of this enzyme includes potent effects of insulin, cAMP, dexamethasone, and glucose (21)(22)(23)32,33), which all may be altered by dietary manipulations. Thus, we used nicotinic acid and lipid infusions to generate various concentrations of circulating lipids while controlling other hormonal and metabolic parameters.…”

Section: Discussionmentioning

confidence: 99%

Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

et al. 1997

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The distal enzymatic step in the process of glucose output is catalyzed by the glucose-6-phosphatase (Glc-6-Pase) complex. The recently cloned catalytic unit of this complex has been shown to be regulated by insulin, dexamethasone, cAMP, and glucose. Using a combination of intralipid and/or nicotinic acid infusions and a pancreatic clamp technique, we maintained plasma free fatty acids (FFAs) at three different levels (0.26 ± 0.07, 0.56 ± 0.09, and 1.59 ± 0.12 mmol/1) in the presence of well-controlled hormonal and metabolic conditions. An increase in the plasma FFA concentration within the physiological range caused a rapid, greater than threefold increase in the mRNA and protein levels of the catalytic subunit of Glc-6-Pase in the liver. These data indicate that the in vivo gene expression of Glc-6-Pase in the liver is regulated by circulating lipids independent of insulin and thus that prolonged hyperlipidemia may contribute to the increased production of glucose via increased expression of this protein. G lucose-6-phosphatase (Glc-6-Pase) catalyzes the final enzymatic step for hepatic gluconeogenesis and glycogenolysis (1). Glc-6-Pase is a complex of proteins with the catalytic portion deeply embedded in the endoplasmic reticulum (ER) (1). Because of its intracellular localization, it has long been suggested that the lipid composition of the ER membrane would play a pivotal role in the regulation of Glc-6-Pase activity. Indeed, some recent reports have shown an acute inhibitory effect of fatty acyl-CoA (2,3) and fatty acid ester (4,5) on Glc-6-Pase activity. In contrast, increased hepatic Glc-6-Pase activity has been reported to follow prolonged increases in dietary saturated fatty acids (6).Important interactions between glucose and lipid metabolism have been demonstrated in skeletal muscle (7-9), liver (8-10), and 3-cells (11). In particular, numerous studies have shown that the rate of endogenous glucose production is closely related to the circulating plasma FFA concentrations ER, endoplasmic reticulum; FFA, free fatty acid; PMSF, phenylmethylsulfonyl fluoride; SSC, sodium chloride-sodium citrate. (9,10,12,13) and that the majority of individuals with NIDDM have increased 24-h plasma FFA profiles (14). While the acute effects of an increase in plasma FFA availability are likely to be largely caused by its known stimulatory effect on gluconeogenesis (15), much less is known regarding the long-term consequences of increased hepatic availability of FFAs.Indeed, dietary fatty acids have been shown to regulate the gene expression of pancreatic GLUT2 and glucokinase (16), and long-chain fatty acids can induce the expression of the genes for the adipocyte fatty acid-binding protein aP2 (17) and liver carnitine palmitoyltransferase I (CPT I) (18). Additionally, the expression of a number of hepatic lipogenic, glycolytic, and gluconeogenic genes is regulated by polyunsaturated fatty acids at the transcriptional level (19,20).Since Glc-6-Pase mRNA and activity increase in metabolic conditions associated with high ...

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“…In addition, GCs were shown to augment endogenous glucose production in several (Rizza et al 1982, Pagano et al 1983, Rooney et al 1993 but not all (Wajngot et al 1990) studies conducted in healthy humans. GC-driven glucose production may be caused by enhanced gluconeogenesis, as GCs induce rate-limiting enzymes for gluconeogenesis, e.g., phosphoenolpyruvate carboxykinase and glucose-6-phosphatase (Lange et al 1994, Cassuto et al 2005; Fig. 1).…”

Section: Hepatic Tissuementioning

confidence: 99%

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

Rafacho¹,

Ortsäter²,

Nadal³

et al. 2014

Journal of Endocrinology

177

114

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Glucocorticoids (GCs) are broadly prescribed for numerous pathological conditions because of their anti-inflammatory, antiallergic and immunosuppressive effects, among other actions. Nevertheless, GCs can produce undesired diabetogenic side effects through interactions with the regulation of glucose homeostasis. Under conditions of excess and/or long-term treatment, GCs can induce peripheral insulin resistance (IR) by impairing insulin signalling, which results in reduced glucose disposal and augmented endogenous glucose production. In addition, GCs can promote abdominal obesity, elevate plasma fatty acids and triglycerides, and suppress osteocalcin synthesis in bone tissue. In response to GC-induced peripheral IR and in an attempt to maintain normoglycaemia, pancreatic b-cells undergo several morphofunctional adaptations that result in hyperinsulinaemia. Failure of b-cells to compensate for this situation favours glucose homeostasis disruption, which can result in hyperglycaemia, particularly in susceptible individuals. GC treatment does not only alter pancreatic b-cell function but also affect them by their actions that can lead to hyperglucagonaemia, further contributing to glucose homeostasis imbalance and hyperglycaemia. In addition, the release of other islet hormones, such as somatostatin, amylin and ghrelin, is also affected by GC administration. These undesired GC actions merit further consideration for the design of improved GC therapies without diabetogenic effects. In summary, in this review, we consider the implication of GC treatment on peripheral IR, islet function and glucose homeostasis.

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Isolation of a cDNA for the Catalytic Subunit of Rat Liver Glucose-6-Phosphatase: Regulation of Gene Expression in FAO Hepatoma Cells by Insulin, Dexamethasone and cAMP

Cited by 119 publications

References 0 publications

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Cortisol in tissue and systemic level as a contributing factor to the development of metabolic syndrome in severely obese patients

Induction of Hepatic Glucose-6-Phosphatase Gene Expression by Lipid Infusion

Glucocorticoid treatment and endocrine pancreas function: implications for glucose homeostasis, insulin resistance and diabetes

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