Islet-cell dysfunction induced by glucocorticoid treatment: potential role for altered sympathovagal balance?

TY - JOUR

T1 - Islet-cell dysfunction induced by glucocorticoid treatment

T2 - potential role for altered sympathovagal balance?

AU - van Raalte, Daniël H

AU - Kwa, Kelly A A

AU - van Genugten, Renate E

AU - Tushuizen, Maarten E

AU - Holst, Jens Juul

AU - Deacon, Carolyn F

AU - Karemaker, John M

AU - Heine, Robert J

AU - Mari, Andrea

AU - Diamant, Michaela

N1 - Copyright © 2013 Elsevier Inc. All rights reserved.

PY - 2013/4

Y1 - 2013/4

N2 - Aim: Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system. Design and Methods: A randomized, placebo-controlled, double-blind, dose-response intervention study was conducted in 32 healthy males (age: 21 ± 2 years; BMI: 21.9 ± 1.7 kg/m2). Participants were allocated to prednisolone 7.5 mg once daily (n = 12), prednisolone 30 mg once daily (n = 12), or placebo (n = 8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test. Results: We found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUC CP): - 2.8 (- 5.2;0.2) and - 3.1 (- 8.8; - 1.0) nmol L- 1 min- 1 for prednisolone 7.5 mg and prednisolone 30 mg, respectively (P = 0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P = 0.001), whereas postprandial glucagon levels were only increased by prednisolone 30 mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r = - 0.407; P = 0.03) and showed a trend towards correlation with fasting glucagon concentrations (r = - 0.337; P = 0.07). The change in sympathovagal balance was inversely related to ASI-iAUCCP (r = - 0.365; P = 0.05). Conclusion: We conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects.

AB - Aim: Glucocorticoids impair glucose tolerance by inducing insulin resistance. We investigated the dose-dependent effects of glucocorticoid treatment on islet-cell function in healthy males and studied the role of the autonomic nervous system. Design and Methods: A randomized, placebo-controlled, double-blind, dose-response intervention study was conducted in 32 healthy males (age: 21 ± 2 years; BMI: 21.9 ± 1.7 kg/m2). Participants were allocated to prednisolone 7.5 mg once daily (n = 12), prednisolone 30 mg once daily (n = 12), or placebo (n = 8) for two weeks. Beta-cell function was measured by hyperglycemic clamp with arginine stimulation, glucagon levels were measured following a standardized meal test. Results: We found that prednisolone treatment dose-dependently reduced C-peptide secretion following arginine stimulation on top of hyperglycemia (ASI-iAUC CP): - 2.8 (- 5.2;0.2) and - 3.1 (- 8.8; - 1.0) nmol L- 1 min- 1 for prednisolone 7.5 mg and prednisolone 30 mg, respectively (P = 0.035 vs. placebo). Fasting glucagon levels increased dose-dependently (vs. placebo; P = 0.001), whereas postprandial glucagon levels were only increased by prednisolone 30 mg. Changes in parasympathetic activity related with changes in fasting glucose levels (r = - 0.407; P = 0.03) and showed a trend towards correlation with fasting glucagon concentrations (r = - 0.337; P = 0.07). The change in sympathovagal balance was inversely related to ASI-iAUCCP (r = - 0.365; P = 0.05). Conclusion: We conclude that in addition to inducing insulin resistance, prednisolone treatment dose-dependently impaired islet-cell function. Altered sympathovagal balance may be related to these effects.

KW - Adolescent

KW - Adult

KW - Anthropometry

KW - Arginine

KW - Blood Glucose

KW - Dose-Response Relationship, Drug

KW - Double-Blind Method

KW - Glucagon

KW - Glucocorticoids

KW - Glucose Clamp Technique

KW - Heart Rate

KW - Humans

KW - Hyperglycemia

KW - Incretins

KW - Islets of Langerhans

KW - Male

KW - Pancreatic Diseases

KW - Pancreatic Function Tests

KW - Prednisolone

KW - Stimulation, Chemical

KW - Sympathetic Nervous System

KW - Vagus Nerve

KW - Young Adult

U2 - 10.1016/j.metabol.2012.10.007

DO - 10.1016/j.metabol.2012.10.007

M3 - Journal article

C2 - 23164480

SN - 0026-0495

VL - 62

SP - 568

EP - 577

JO - Metabolism

JF - Metabolism

IS - 4

ER -