Hormonal regulation of key gluconeogenic enzymes and glucose release in cultured hepatocytes: Effects of dexamethasone and gastrointestinal hormones on glucagon action

Noether-Fleig, Gaby; Roeben, Heidemarie; Ditschuneit, H.

doi:10.1016/0003-9861(84)90164-4

Cited by 34 publications

(17 citation statements)

References 65 publications

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“…This determination was based on estimating the Previous data derived under similar conditions but analyzed using a different approach failed to reveal significant enhancement in gluconeogenesis by steroid treatment (15). This conclusion remained largely at odds with in vitro data demonstrating stimulatory effects of cortisol on phosphoenolpyruvate carboxykinase (PEPCK) activity (44) and PEPCK mRNA transcription (10). In the former study (15) and in the present study, neither gluconeogenic efficiency nor the GNG max was significantly increased by steroid treatment.…”

Section: Discussioncontrasting

confidence: 56%

“…Although the steroid treatment increased hepatic gluconeogenesis, the treatment also caused a significant increase in R a , thus accounting for the failure of hepatic GNG flux (39%) to increase as a percentage of total R a . Hellerstein and colleagues (19,20,21) and Neese and colleagues (41,42) have recently assessed gluconeogenesis by mass isotopomer distribution analysis by use of [2][3][4][5][6][7][8][9][10][11][12][13] C]glycerol, [3-13 C]lactate, or [1-13 C]lactate. In rats, progressive fasting increased the ratio of gluconeogenesis as a percentage of glucose production from ϳ50% at 5-6 h to 80% at 20-24 h (41).…”

Section: Discussionmentioning

confidence: 99%

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Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Goldstein

Rossetti

Palmer

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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. Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo. Am J Physiol Endocrinol Metab 283: E946-E957, 2002; 10.1152/ajpendo.00320.2002The purpose of this study was to compare the assessment of gluconeogenesis (GNG) in the overnight-and prolonged-fasted states and during chronic hypercortisolemia using the arteriovenous difference and [ 14 C]phosphoenolpyruvate-liver biopsy techniques as well as a combination of the two. Two weeks before a study, catheters and flow probes were implanted in the hepatic and portal veins and femoral artery of dogs. Animals were studied after an 18-h fast (n ϭ 8), a 42-or 66-h fast (n ϭ 7), and an 18-h fast plus a continuous infusion of cortisol (3.0 g⅐kg Ϫ1 ⅐min Ϫ1) for 72 h (n ϭ 7). Each experiment consisted of an 80-min tracer ([3-3 H]glucose and [U-14 C]alanine) and dye equilibration period (Ϫ80 to 0 min) and a 45-min sampling period. In the cortisoltreated group, plasma cortisol increased fivefold. In the overnight-fasted group, total GNG flux rate (GNG flux), conversion of glucose 6-phosphate to glucose (GNG G-6-P3 Glc), glucose cycling, and maximal GNG flux rate (GNG max) were 0.95 Ϯ 0.14, 0.65 Ϯ 0.06, 0.62 Ϯ 0.06, and 0.70 Ϯ 0.09 mg⅐kg Ϫ1 ⅐min Ϫ1, respectively. In the prolonged-fasted group, they were 1.50 Ϯ 0.18, 1.18 Ϯ 0.13, 0.40 Ϯ 0.07, and 1.28 Ϯ 0.10 mg⅐kg Ϫ1 ⅐min Ϫ1, whereas in the cortisol-treated group they were 1.64 Ϯ 0.33, 0.99 Ϯ 0.29, 1.32 Ϯ 0.24, and 0.91 Ϯ 0.13 mg⅐kg Ϫ1 ⅐min Ϫ1. These results demonstrate that GNG G-6-P3 Glc and GNGmax were almost identical. However, these rates were 15-38% lower than GNG flux generated by a combination of the two methods. This difference was most apparent in the steroid-treated group, where the combination of the two methods (GNG flux ) detected a significant increase in gluconeogenic flux.fasting; cortisol THE QUEST TO DEVELOP accurate methods for determining the rate of gluconeogenesis in vivo is ongoing. Many early studies used tracer methods or arteriovenous (a-v) difference techniques to assess the gluconeogenic rate in vivo (12,23,27,28). In 1977, Chiasson et al. (5) combined these two approaches for the assessment of gluconeogenesis in the dog. The latter approach yielded two estimates of gluconeogenesis, the gluconeogenic efficiency (percent extracted gluconeogenic carbon converted to glucose) and the gluconeogenic conversion rate (the rate of glucose production from the gluconeogenic precursor given). Both represented minimal estimates of gluconeogenesis due largely to dilution of the tracer in the oxaloacetate (OAA) pool of the liver (25). This approach was further extended by calculating the minimal and maximal rates of gluconeogenesis from circulating gluconeogenic precursors (3, 16, 51). The maximal rate was derived by measuring the net hepatic uptakes of all gluconeogenic precursors using the a-v difference technique and assuming that they were quantitatively converted to glucose. The minimal rate was derived by multiplying the maximal rate of gluconeog...

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Section: Discussioncontrasting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Goldstein

Rossetti

Palmer

et al. 2002

American Journal of Physiology-Endocrinology and Metabolism

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“…Gluconeogenic conversion of alanine to glucose has been demonstrated to be increased during acute rises in plasma cortisol (19). Furthermore, phosphoenolpyruvate carboxykinase (PEPCK) activity is increased by glucocorticoids, consistent with an increase in gluconeogenesis during hypercortisolemia (16). As pointed out by Sasaki et al (44), dexamethasoneinduced increase of PEPCK gene transcription is either blunted or totally inhibited by elevated insulin, suggesting that insulin is a dominant hormone in the regulation of gluconeogenesis (44).…”

Section: Discussionmentioning

confidence: 93%

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

Nielsen¹,

Caumo²,

Chandramouli³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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, September , 2011; 34 (9): 1959-1964 has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion with hydrocortisone or saline. Glucose effectiveness was assessed by a combined somatostatin and insulin infusion protocol to maintain insulin concentration at basal level in the presence of prandial glucose infusions. Despite elevated insulin concentrations (P Ͻ 0.05), hypercortisolemia resulted in higher glucose (P Ͻ 0.05) and free fatty acid concentrations (P Ͻ 0.05). Furthermore, basal insulin concentrations were higher during hydrocortisone than during saline infusion (P Ͻ 0.01), indicating the presence of steroidinduced insulin resistance. Postabsorptive glucose production (P ϭ 0.64) and the fractional contribution of gluconeogenesis to EGR (P ϭ 0.33) did not differ on the two study days. During the prandial glucose infusion, the integrated glycemic response above baseline was higher in the presence of hydrocortisone than during saline infusion (P Ͻ 0.05), implying a decrease in net glucose effectiveness (4.42 Ϯ 0.52 vs. 6.65 Ϯ 0.83 ml⅐kg Ϫ1 ⅐min Ϫ1 ; P Ͻ 0.05). To determine whether this defect is attributable to an impaired ability of glucose to suppress glucose production, to stimulate its own uptake, or both, glucose turnover and "hot" (labeled) indexes of glucose effectiveness (GE) were calculated. Hepatic GE was lower during cortisol than during saline infusion (2.39 Ϯ 0.24 vs. 3.82 Ϯ 0.51 ml⅐kg Ϫ1 ⅐min Ϫ1 ; P Ͻ 0.05), indicating a defect in the ability of glucose to restrain its own production. In addition, in the presence of excess cortisol, glucose disappearance was inappropriate for the prevailing glucose concentration, implying a decrease in glucose clearance (P Ͻ 0.05). The decrease in glucose clearance was confirmed by the higher increment in [3-3 H]glucose during hydrocortisone than during saline infusion (P Ͻ 0.05), despite the administration of identical tracer infusion rates. In conclusion, short-term hypercortisolemia in healthy individuals with normal ␤-cell function decreases insulin action but does not alter rates of EGR and gluconeogenesis. In addition, cortisol impairs the ability of glucose to suppress its own production, which due to accumulation of glucose in the glucose space results in impaired peripheral glucose clearance. These results suggest that cortisol excess

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“…To analyze that relative rates of glucose [20]. Both glucagon and dexamethasone have been shown to be potent mediators of PEP-CK activity in consumption and production in hepatocytes in cancer, we analyzed rates of both glucose oxidation and glucose isolated hepatoyctes, upregulating the activity of this important gluconeogenic enzyme [21]. It is likely that production when tumors comprised 5 and 15% of body weight.…”

Section: Resultsmentioning

confidence: 99%

Alterations in Oxidative Metabolism and Glutamine Transport Support Glucose Production in the Tumor-Influenced Hepatocyte

Fischer¹,

Bode

Hurley

et al. 1997

Journal of Surgical Research

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Hormonal regulation of key gluconeogenic enzymes and glucose release in cultured hepatocytes: Effects of dexamethasone and gastrointestinal hormones on glucagon action

Cited by 34 publications

References 65 publications

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Effects of fasting and glucocorticoids on hepatic gluconeogenesis assessed using two independent methods in vivo

Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

Alterations in Oxidative Metabolism and Glutamine Transport Support Glucose Production in the Tumor-Influenced Hepatocyte

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