Role of counterregulatory hormones in the catabolic response to stress.

Gelfand, R; Matthews, Dwight E.; Bier, Dennis M.; Sherwin, Robert S.

doi:10.1172/jci111650

Cited by 222 publications

(71 citation statements)

References 54 publications

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“…The protein oxidation rate was also normalised by combined transplantation (Table 3). Although prednisone has been shown to increase protein catabolism [58][59][60][61] our prednisone-treated groups showed normal protein catabolic rates, again probably explained by the low dose of this drug administered.…”

Section: Discussionmentioning

confidence: 71%

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

et al. 1990

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Summary.To evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry. Nine of the original 15 patients were studied again after four months and six after 12 months, successful combined kidney-pancreas transplantation with the same experimental protocol. Nine volunteers formed the group of normal subjects. Combined kidney-pancreas transplantation normalised hepatic glucose production and reduced peripheral insulin resistance in Type 1 diabetic uraemic patients, despite chronic immunosuppressive therapy. To further evaluate the hypothesis that residual insulin resistance was due to chronic steroid therapy, 11 additional subjects with chronic uveitis (six of whom were treated with only prednisone, and five treated only with cyclosporin) underwent the same protocol demonstrating a normal hepatic glucose production. The insulin-stimulated peripheral glucose uptake was reduced in the prednisonetreated group, but normal in cyclosporin-treated subjects. Four additional diabetic patients with a kidney transplant were also studied. They showed a peripheral insulin sensitivity intermediate between diabetic uraemic patients and patients after combined transplant. We conclude that shortterm (one year) combined kidney-pancreas transplantation improves glucose metabolism by restoring normal rates of hepatic glucose production and reducing peripheral insulin resistance; chronic steroid therapy is the major determinant of residual reduced insulin action. Both kidney and pancreas substitution play a role in reducing peripheral insulin resistance.

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Section: Discussionmentioning

confidence: 71%

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

et al. 1990

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“…These cytokines trigger the expression of CRP, PCT, ProADM and WBC as part of the immune response [35][36][37][38][39][40][41]. Also, severe illness and systemic infection activate the sympathoadrenal system and the hypothalamic-pituitary-adrenal axis [42][43][44][45], which causes peripheral insulin resistance, ultimately leading to hyperglycaemia [42]. To study the effects of hyperglycaemia on outcomes, we adjusted the analysis for CAP severity.…”

Section: Discussionmentioning

confidence: 99%

Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study

et al. 2013

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Aims/hypothesis Despite the condition's high prevalence, the influence of hyperglycaemia on clinical outcomes in noncritical-care inpatients with infections remains ill defined. In this study, we analysed associations of glucose levels at admission and during initial inpatient treatment with the inflammatory response and clinical outcome in communityacquired pneumonia (CAP) patients. Methods This secondary observational analysis included 880 confirmed CAP patients. We used severity-adjusted multivariate regression models to investigate associations of initial and 96 h mean glucose levels with serially measured biomarker levels over 7 days (C-reactive protein [CRP], procalcitonin, white blood cell count [WBC], pro-adrenomedullin [ProADM]) and adverse clinical course (death and intensivecare unit admission). Results In the 724 non-diabetic patients (82.3% of the study population), moderate or severe hyperglycaemia (glucose 6-11 mmol/l and >11 mmol/l, respectively) was associated with increased risk for adverse clinical course (adjusted OR [95% CI] 1.4 [0.8, 2.4] and 3.0 [1.1, 8.0], respectively) and with higher CRP, WBC and ProADM levels over 7 days (p <0.05, ANOVA, all days). In diabetic patients (n =156), no similar associations were found for initial hyperglycaemia, although mean 96 h glucose levels ≥9 mmol/l were associated with adverse clinical course (adjusted OR 5.4 [1.1, 25.8]; p =0.03). No effect modification by insulin treatment was detected (interaction terms p >0.2 for all analyses). Conclusions/interpretation Initial hyperglycaemia in nondiabetic CAP patients, and prolonged hyperglycaemia in diabetic or non-diabetic CAP patients, are associated with a more pronounced inflammatory response and CAP-related adverse clinical outcome. Optimal glucose targets for insulin treatment of hyperglycaemia in non-critical-care settings should be defined.

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“…The cytokine response to trauma and sepsis can be variable, depending on the nature of the assault. The hormonal infusion studies simulating stress have been useful in providing an insight into the mechanisms that regulate substrate metabolism (Gelfand et al 1984). However, it has to be appreciated that while hormonal infusion studies may provide insight into various regulatory mechanisms they have not been able to account for all the metabolic effects seen in sepsis and trauma (Frayn, 1986).…”

Section: Regulation Of Lipid Metabolism During Sepsis and Traumamentioning

confidence: 99%

Regulation of lipid metabolism in adipose tissue

Samra

2000

Proc. Nutr. Soc.

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Adipose tissue is a major source of metabolic fuel. This metabolic fuel is stored in the form of triacylglycerol. Lipolysis of triacylglycerol yields non-esterified fatty acids and glycerol. In human subjects in vivo studies of the regulation of lipid metabolism in adipose tissue have been difficult because of the heterogeneous nature of the tissue and lack of a vascular pedicle. In the last decade the methodology of study of adipose tissue has improved with the advent of the anterior abdominal wall adipose tissue preparation technique and microdialysis. These techniques have demonstrated that lipid metabolism in adipose tissue is finely coordinated during feeding and fasting cycles, in order to provide metabolic fuel when required. Lipolysis takes place both in extracellular and intracellular space. The extracellular lipolysis is regulated by lipoprotein lipase and the intracellular lipolysis is regulated by hormone-sensitive lipase. In pathophysiological conditions such as trauma, sepsis and starvation profound changes are induced in the regulation of lipid metabolism. The increased mobilization of lipid fuel is brought about by the differential actions of various counter-regulatory hormones on adipose tissue blood flow and adipose tissue lipolysis through lipoprotein lipase and hormone-sensitive lipase, resulting in increased availability of non-esterified fatty acids as a source of fuel. In recent years, it has been demonstrated that adipose tissue produces various cytokines and these cytokines can have paracrine and endocrine effects. It would appear that adipose tissue has the ability to regulate lipid metabolism locally as well as at distant sites such as liver, muscle and brain. In future, it is likely that the mechanisms that lead to the secondary effects of lipid metabolism on atheroma, immunity and carcinogenesis will be demonstrated.

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Role of counterregulatory hormones in the catabolic response to stress.

Cited by 222 publications

References 54 publications

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

Reduction of insulin resistance by combined kidney-pancreas transplantation in Type 1 (insulin-dependent) diabetic patients

Effect of hyperglycaemia on inflammatory and stress responses and clinical outcome of pneumonia in non-critical-care inpatients: results from an observational cohort study

Regulation of lipid metabolism in adipose tissue

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