Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action

R. A. Rizza, L. J. Mandarino, J. E. Gerich

Research output: Contribution to journalArticle

516 Citations (Scopus)

Abstract

The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 μg kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 ± 3 vs. 14 ± 1 μg/dl; P < 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 ± 2 vs. 97 ± 2 mg/dl; P < 0.01) and plasma insulin (16 ± 2 vs. 10 ± 2 μU/ml; P < 0.01) concentrations and rates of glucose production (2.4 ± 0.1 vs. 2.1 ± -0.1 mg kg-1 min-1; P < 0.01) and utilization (2.5 ± 0.1 vs. 2.1 ± 0.1 mg kg-1 min-1; P < 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 ± 19 vs. 31 ± 5 μU/ml; P < 0.05) and stimulation of glucose utilization (half-maximal response at 104 ± 9 vs. 64 ± 7 μU/ml; P < 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man is due to a decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.

Original languageEnglish (US)
Pages (from-to)131-138
Number of pages8
JournalJournal of Clinical Endocrinology and Metabolism
Volume54
Issue number1
StatePublished - 1982
Externally publishedYes

Fingerprint

Insulin Resistance
Hydrocortisone
Insulin
Glucose
Defects
Monocytes
Insulin Receptor
Erythrocytes
Plasmas
Erythrocyte Count
Healthy Volunteers
Liver
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{5e149f9cf75940698d4d8104b1082a13,
title = "Cortisol-induced insulin resistance in man: Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action",
abstract = "The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 μg kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 ± 3 vs. 14 ± 1 μg/dl; P < 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 ± 2 vs. 97 ± 2 mg/dl; P < 0.01) and plasma insulin (16 ± 2 vs. 10 ± 2 μU/ml; P < 0.01) concentrations and rates of glucose production (2.4 ± 0.1 vs. 2.1 ± -0.1 mg kg-1 min-1; P < 0.01) and utilization (2.5 ± 0.1 vs. 2.1 ± 0.1 mg kg-1 min-1; P < 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 ± 19 vs. 31 ± 5 μU/ml; P < 0.05) and stimulation of glucose utilization (half-maximal response at 104 ± 9 vs. 64 ± 7 μU/ml; P < 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man is due to a decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.",
author = "Rizza, {R. A.} and Mandarino, {L. J.} and Gerich, {J. E.}",
year = "1982",
language = "English (US)",
volume = "54",
pages = "131--138",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "The Endocrine Society",
number = "1",

}

TY - JOUR

T1 - Cortisol-induced insulin resistance in man

T2 - Impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action

AU - Rizza, R. A.

AU - Mandarino, L. J.

AU - Gerich, J. E.

PY - 1982

Y1 - 1982

N2 - The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 μg kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 ± 3 vs. 14 ± 1 μg/dl; P < 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 ± 2 vs. 97 ± 2 mg/dl; P < 0.01) and plasma insulin (16 ± 2 vs. 10 ± 2 μU/ml; P < 0.01) concentrations and rates of glucose production (2.4 ± 0.1 vs. 2.1 ± -0.1 mg kg-1 min-1; P < 0.01) and utilization (2.5 ± 0.1 vs. 2.1 ± 0.1 mg kg-1 min-1; P < 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 ± 19 vs. 31 ± 5 μU/ml; P < 0.05) and stimulation of glucose utilization (half-maximal response at 104 ± 9 vs. 64 ± 7 μU/ml; P < 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man is due to a decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.

AB - The present studies were undertaken to assess the mechanisms responsible for cortisol-induced insulin resistance in man. The insulin dose-response characteristics for suppression of glucose production and stimulation of glucose utilization and their relationship to monocyte and erythrocyte insulin receptor binding were determined in six normal volunteers after 24-h infusion of cortisol and 24-h infusion of saline. The infusion of cortisol (2 μg kg-1 min-1) increased the plasma cortisol concentration approximately 4-fold (37 ± 3 vs. 14 ± 1 μg/dl; P < 0.01) to values observed during moderately severe stress in man. This hypercortisolemia increased postabsorptive plasma glucose (126 ± 2 vs. 97 ± 2 mg/dl; P < 0.01) and plasma insulin (16 ± 2 vs. 10 ± 2 μU/ml; P < 0.01) concentrations and rates of glucose production (2.4 ± 0.1 vs. 2.1 ± -0.1 mg kg-1 min-1; P < 0.01) and utilization (2.5 ± 0.1 vs. 2.1 ± 0.1 mg kg-1 min-1; P < 0.01). Insulin dose-response curves for both suppression of glucose production (half-maximal response at 81 ± 19 vs. 31 ± 5 μU/ml; P < 0.05) and stimulation of glucose utilization (half-maximal response at 104 ± 9 vs. 64 ± 7 μU/ml; P < 0.01) were shifted to the right, with preservation of normal maximal responses to insulin. Neither monocyte nor erythrocyte insulin binding was decreased. However, except at near-maximal insulin receptor occupancy, the action of insulin on glucose production and utilization per number of monocyte and erythrocyte insulin receptors occupied was decreased. These results indicate that the cortisol-induced insulin resistance in man is due to a decrease in both hepatic and extrahepatic sensitivity to insulin. Assuming that insulin binding to monocytes and erythrocytes reflects insulin binding in insulin-sensitive tissues, this decrease in insulin action can be explained on the basis of a postreceptor defect.

UR - http://www.scopus.com/inward/record.url?scp=0020469555&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020469555&partnerID=8YFLogxK

M3 - Article

C2 - 7033265

VL - 54

SP - 131

EP - 138

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 1

ER -