Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog

Fujiwara, Toshihiko; Cherrington, Alan D.; Neal, Doss; McGuinness, Owen P.

doi:10.1016/s0026-0495(96)90026-8

Cited by 52 publications

(36 citation statements)

References 23 publications

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“…Consistent with those results, our data show that even after prolonged 11␤-HSD1 inhibition it was hepatic glycogen metabolism, not gluconeogenic flux, that was affected by 11␤-HSD1 inhibition. However, it remains possible that gluconeogenesis might be reduced under other circumstances, such as when the gluconeogenic precursor supply is elevated (23,37). Nevertheless, the initial glycogenolytic surge that occurred in the control group was completely absent in the presence of the inhibitor such that net hepatic glycogenolysis remained suppressed throughout the study period despite elevated glucagon and epinephrine levels.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, however, both phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) mRNA levels decreased, raising the possibility that gluconeogenesis would have been reduced had enough time for meaningful changes in the levels of those enzymes been allowed. Therefore, the purpose of this study was to examine the effect of 7 days of 11␤-HSD1 inhibition on basal glucose metabolism and on the metabolic responses to a hormonal challenge known to augment HGP by increasing gluconeogenesis and glycogenolysis (23,25). …”

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confidence: 99%

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Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis

Winnick

Ramnanan

Saraswathi

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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The aim of this study was to determine the effect of prolonged 11␤-hydroxysteroid dehydrogenase-1 (11␤-HSD1) inhibition on basal and hormone-stimulated glucose metabolism in fasted conscious dogs. For 7 days prior to study, either an 11␤-HSD1 inhibitor (HSD1-I; n ϭ 6) or placebo (PBO; n ϭ 6) was administered. After the basal period, a 4-h metabolic challenge followed, where glucagon (3ϫ-basal), epinephrine (5ϫ-basal), and insulin (2ϫ-basal) concentrations were increased. Hepatic glucose fluxes did not differ between groups during the basal period. In response to the metabolic challenge, hepatic glucose production was stimulated in PBO, resulting in hyperglycemia such that exogenous glucose was required in HSD-I (P Ͻ 0.05) to match the glycemia between groups. Net hepatic glucose output and endogenous glucose production were decreased by 11␤-HSD1 inhibition (P Ͻ 0.05) due to a reduction in net hepatic glycogenolysis (P Ͻ 0.05), with no effect on gluconeogenic flux compared with PBO. In addition, glucose utilization (P Ͻ 0.05) and the suppression of lipolysis were increased (P Ͻ 0.05) in HSD-I compared with PBO. These data suggest that inhibition of 11␤-HSD1 may be of therapeutic value in the treatment of diseases characterized by insulin resistance and excessive hepatic glucose production.11␤-hydroxysteroid dehydrogenase-1; cortisol; hepatic glucose production; glycogenolysis; gluconeogenesis CORTISOL IS A STEROID HORMONE with many physiological effects, including the regulation of carbohydrate, protein, and fat metabolism. At pathological concentrations, cortisol produces metabolic abnormalities similar to the metabolic syndrome, including obesity, insulin resistance, fasting hyperglycemia, hypertension, and dyslipidemia (2,42,56,58). In vivo cortisol action can be modified by 11␤-hydroxysteroid dehydrogenase-1 (11␤-HSD1), an enzyme that converts intracellular cortisone into active cortisol without necessarily modifying plasma cortisol concentrations (4, 6, 59). Liver (55, 57) and adipose (30, 33) 11␤-HSD1 activity has been shown to be elevated in obese humans with type 2 diabetes mellitus and the metabolic syndrome, and an intracellular Cushings-like state may contribute to these abnormalities (28, 32). In mice, hepatic 11␤-HSD1 overexpression can increase hepatic lipid flux, thereby causing dyslipidemia and insulin resistance (46), whereas overexpression in adipose tissue causes obesity, impaired glucose tolerance, and hypertension (35, 36). Conversely, when the enzyme is knocked out or acutely inhibited, mouse models of diabetes are protected against the manifestations of the metabolic syndrome (1, 31, 43). Together, these data demonstrate an overarching ability of dysregulated cortisol metabolism to generate a phenotype similar to that of type 2 diabetes and illustrate the potential therapeutic value of 11␤-HSD1 inhibition in the treatment of insulin resistance.Cortisol has potent effects on the glucoregulatory actions of hormones that regulate hepatic glucose production (HGP). For example, cortisol has been...

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis

Winnick

Ramnanan

Saraswathi

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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“…In order to increase circulating glucose levels, cortisol is postulated to increase the levels and activities of several glycogenolysis enzymes in hepatocytes (Mommsen et al, 1999). Additionally, cortisol may increase gluconeogenic activity in the liver and promote the release of gluconeogenic precursors from protein and lipid stores within the body (Fujiwara et al, 1996). Furthermore, cortisol stimulates gill Na'IK' -ATPase activities and chloride cell proliferation, which in stressed saltwater fish pumps…”

Section: : Exhaustionmentioning

confidence: 99%

The effects of diet composition and ration on biotransformation enzymes and stress parameters in rainbow trout, Oncorhynchus mykiss

Morrow

Higgs

Kennedy

2004

Comparative Biochemistry and Physiology Part C: Toxicology &

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Degree:Master of ~nvironmentai ToxicologyTitle of Project:The effects of diet composition and ration on biotransformation enzymes and stress parameters in rainbow trout, Oncorhynchus mykiss. PARTIAL COPYRIGHT LICENCEI hereby grant to Simon Fraser University the right to lend my thesis, project or extended essay (the title of which is shown below) to users of the Simon Fraser University Library, and to make partial or single copies only for such users or in response to a request from the library of any other university, or other educational institution, on its own behalf or for one of its users. I further agree that permission for multiple copying of this work for scholarly purposes may be granted by me or the Dean of Graduate Studies. It is understood that copying or publication of this work for financial gain shall not be allowed without my written permission. Title of ThesislProjecff Extended EssayThe effects of diet composition and ration on biotransforrnation enzymres and stress parameters in rainbow trout, Oncorhynchus mykiss.Michelle Dayna Morrow (name) ABSTRACTNutritional quality and quantity play significant roles in the amount of energy an animal assimilates and in the distribution of that energy. Furthermore, energy is allocated in a hierarchical fashion beginning with basal metabolism and then successively to other physiological processes depending on other energetic requirements of the animal. To date, little information exists on the effects of diet and ration on the stress response and detoxification system in fish. Therefore, the purpose of this study was to measure the effects of dietary composition and ration on the biotransformation and stress response systems in juvenile rainbow trout.Juvenile rainbow trout (Oncorhynchus mykiss) were fed one of three isoenergetic diets varying in protein (35 to 55%) and lipid content (8 to 18%), at full satiation or partial ration for 6 weeks in order to investigate the effects of diet on baseline stress parameters and biotransformation enzyme activity. Growth was highest in fish fed low protein, high lipid diets at both ration levels and was highest overall in fish fed to satiation. Stress indicators, including plasma lactate, glucose and cortisol concentrations were not significantly affected by dietary treatment or ration. Basal biotransformation enzyme activity, including glutathione S-transferase (GST) and ethoxyresorufin 0-deethylase (EROD) activity, were also unaffected by dietary treatment. Fish exposed to the biotransformation enzyme inducer 13-napthoflavone did not exhibit an alteration in stress indicators or GST activity; however, EROD activity was increased (87 to 210-fold) in fish receiving all diets and rations demonstrating the importance of this system even under limited energy intake.The results of the present study indicate that, unlike mammals, fish may be more recalcitrant to different levels of ingestion (above maintenance ration) of isoenergetic ACKNOWLEDGEMENTS

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“…The potential impact of elevations in these counterregulatory hormones is supported by experimental evidence in humans and animals that stress can induce hyperglycemia (41). The balance between catecholamines, glucocorticoids, and glucagon can have distinct effects on glycogenolysis, gluconeogenesis, and glucose flux across specific tissues (18,21), such that, depending on its nature and duration, stress could confound the characterization of metabolic as well as hormonal aspects of counterregulation. Therefore, glucose clamp techniques that minimize potential confounding effects of stress on counterregulatory responses are needed in mice.…”

mentioning

confidence: 99%

Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice

Jacobson¹,

Ansari²,

McGuinness³

2006

American Journal of Physiology-Endocrinology and Metabolism

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Jacobson, Lauren, Tasneem Ansari, and Owen P. McGuinness. Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice. Am J Physiol Endocrinol Metab 290: E678 -E684, 2006; doi: 10.1152/ajpendo.00383.2005.-Hypoglycemia-induced counterregulatory failure is a dangerous complication of insulin use in diabetes mellitus. Controlled hypoglycemia studies in gene knockout models, which require the use of mice, would aid in identifying causes of defective counterregulation. Because stress can influence counterregulatory hormones and glucose homeostasis, we developed glucose clamps with remote blood sampling in conscious, unrestrained mice. Male C57BL/6 mice implanted with indwelling carotid artery and jugular vein catheters were subjected to 2 h of hyperinsulinemic glucose clamps 24 h apart, with a 6-h fast before each clamp. On day 1, blood glucose was maintained (euglycemia, 178 Ϯ 4 mg/dl) or decreased to 62 Ϯ 1 mg/dl (hypoglycemia) by insulin (20 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) and variable glucose infusion. Donor blood was continuously infused to replace blood sample volume. Baseline plasma epinephrine (32 Ϯ 8 pg/ml), corticosterone (16.1 Ϯ 1.8 g/dl), and glucagon (35 Ϯ 3 pg/ml) were unchanged during euglycemia but increased significantly during hypoglycemia, with a glycemic threshold of ϳ80 mg/dl. On day 2, all mice underwent a hypoglycemic clamp (blood glucose, 64 Ϯ 1 mg/dl). Compared with mice that were euglycemic on day 1, previously hypoglycemic mice had significantly higher glucose requirements and significantly lower plasma glucagon and corticosterone (n ϭ 6/group) on day 2. Epinephrine tended to decrease, although not significantly, in repeatedly hypoglycemic mice. Pre-and post-clamp insulin levels were similar between groups. We conclude that counterregulatory responses to acute and repeated hypoglycemia in unrestrained, chronically cannulated mice reproduce aspects of counterregulation in humans, and that repeated hypoglycemia in mice is a useful model of counterregulatory failure.hypoglycemia-associated autonomic failure; hypoglycemia unawareness; catecholamines; norepinephrine; glucocorticoids HYPOGLYCEMIA-ASSOCIATED COUNTERREGULATORY FAILURE is an increasingly common complication of intensive insulin therapy and poses new obstacles to glucose control in insulindependent diabetes. Counterregulatory failure is evident as decreases in either the absolute level or the threshold for activation of sympathoadrenal, glucocorticoid, and glucagon responses to hypoglycemia (3). Of these responses, the glucagon and sympathoadrenal responses are the most critical because of the rapidity with which they are activated and serve to increase blood glucose (4). Counterregulatory failure is not unique to individuals with type 1 diabetes and can be demonstrated experimentally in nondiabetic subjects after only one to two episodes of hypoglycemia (5, 6). However, because type 1 diabetes patients lack the ability to decrease insulin and often lose hypoglycemia-in...

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Role of cortisol in the metabolic response to stress hormone infusion in the conscious dog

Cited by 52 publications

References 23 publications

Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis

Effects of 11β-hydroxysteroid dehydrogenase-1 inhibition on hepatic glycogenolysis and gluconeogenesis

The effects of diet composition and ration on biotransformation enzymes and stress parameters in rainbow trout, Oncorhynchus mykiss

Counterregulatory deficits occur within 24 h of a single hypoglycemic episode in conscious, unrestrained, chronically cannulated mice

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