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Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man.
Clin Nutr. 2000 Feb; 19(1):29-34.CN

Abstract

AIMS

This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon.

METHODS

Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min.

RESULTS

In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time.

CONCLUSION

These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity.

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Authors+Show Affiliations

Dirlewanger M
Institute of Physiology, University of Lausanne, Lausanne, Switzerland.
Schneiter PH
No affiliation info available
Paquot N
No affiliation info available
Jequier E
No affiliation info available
Rey V
No affiliation info available
Tappy L
No affiliation info available

MeSH

AdultDexamethasoneFemaleGlucagonGlucocorticoidsGlucoseHumansHyperinsulinismInfusions, IntravenousInsulinInsulin ResistanceLiverMaleReference ValuesSomatostatinTime Factors

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10700531

Citation

Dirlewanger, M, et al. "Effects of Glucocorticoids On Hepatic Sensitivity to Insulin and Glucagon in Man." Clinical Nutrition (Edinburgh, Scotland), vol. 19, no. 1, 2000, pp. 29-34.
Dirlewanger M, Schneiter PH, Paquot N, et al. Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man. Clin Nutr. 2000;19(1):29-34.
Dirlewanger, M., Schneiter, P. H., Paquot, N., Jequier, E., Rey, V., & Tappy, L. (2000). Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man. Clinical Nutrition (Edinburgh, Scotland), 19(1), 29-34.
Dirlewanger M, et al. Effects of Glucocorticoids On Hepatic Sensitivity to Insulin and Glucagon in Man. Clin Nutr. 2000;19(1):29-34. PubMed PMID: 10700531.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of glucocorticoids on hepatic sensitivity to insulin and glucagon in man. AU - Dirlewanger,M, AU - Schneiter,P H, AU - Paquot,N, AU - Jequier,E, AU - Rey,V, AU - Tappy,L, PY - 2000/3/4/pubmed PY - 2000/7/6/medline PY - 2000/3/4/entrez SP - 29 EP - 34 JF - Clinical nutrition (Edinburgh, Scotland) JO - Clin Nutr VL - 19 IS - 1 N2 - AIMS: This study was undertaken to determine the effects of a short-term dexamethasone treatment on hepatic sensitivities to insulin and glucagon. METHODS: Eleven healthy subjects were studied during one or several of four protocols. In all protocols, somatostatin was infused continuously to inhibit pancreatic hormone secretion. In protocol 1, basal insulin was infused over 300 min while glucagon was infused at a rate of 0.5 mg/kg(-1)/min(-1)during 180 min, then at a rate of 1.5 ng/kg(-1)/min(-1)during 150 min. In protocol 2, the same experiment was performed after a 2 day treatment with 8 mg/day dexamethasone. In protocol 3, the two-step glucagon infusion was performed during insulin infusion at a rate aimed to reproduce the hyperinsulinemia observed during protocol 2. In protocol 4, continuous basal insulin and low glucagon (0.5 mg/kg(-1)/min(-1)) were infused over 330 min. RESULTS: In protocol 1, plasma glucose rose transiently by 2.0 +/- 0.3 mmol/l when the glucagon rate was increased and glucose production increased by 1.4 +/- 0.5 micromol/kg(-1)/min(-1). In protocol 2, the insulin infusion rate (1.85 +/- 0.36 nmol/kg(-1)/min(-1)) required to maintain glycemia was 3.3-fold higher than during protocol 1. Glucagon-induced stimulation of glycemia (by 1.47 +/- 0.5 mmol/l) and endogenous glucose production (by 0.8 +/- 0.3 micromol/kg(-1)/min(-1)) were blunted, but not abolished. In protocol 3, endogenous glucose production was suppressed by 75% by hyperinsulinemia and was not stimulated when the glucagon infusion rate was increased. In protocol 4, endogenous glucose production did not change significantly with time. CONCLUSION: These results indicate that high dose glucocorticoids induce a marked hepatic insulin resistance. Stimulation of glucose production by hyperglucagonemia was maintained in spite of hyperinsulinemia which can be attributed to either hepatic insulin resistance and/or increased hepatic glucagon sensitivity. SN - 0261-5614 UR - https://www.unboundmedicine.com/medline/citation/10700531/Effects_of_glucocorticoids_on_hepatic_sensitivity_to_insulin_and_glucagon_in_man_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0261-5614(99)90064-X DB - PRIME DP - Unbound Medicine ER -