Sympathetic regulation of glucose uptake by the alpha1-adrenoceptor in human obesity

Obes Res. 2004 Apr;12(4):612-20. doi: 10.1038/oby.2004.70.

Abstract

Objective: To investigate the involvement of alpha1-adrenoceptors in the sympathetic regulation of glucose uptake in human adipocytes.

Research methods and procedures: Twenty-four severely obese subjects participated in this study. The microdialysis technique was used to determine interstitial glucose concentration after stimulation of abdominal subcutaneous adipose tissue with the alpha1-agonist norfenefrine, the alpha1,2beta-agonist norepinephrine, and both agents in combination with the alpha1-antagonist urapidil. The effect of beta-adrenoceptor stimulation was assessed by orciprenaline. Changes in local blood flow were determined using the ethanol escape technique.

Results: Both norfenefrine and norepinephrine induced a concentration-dependent decrease of interstitial glucose concentration, with a greater decrease observed with norepinephrine. Preperfusion of adipose tissue with urapidil inhibited glucose decrease. The inhibition was overcome with high concentrations of norfenefrine and norepinephrine, respectively. Both adrenergic agents induced tachyphylaxia. Urapidil enhanced extracellular glucose level at high concentration. Blood flow decreased in the presence of norfenefrine and norepinephrine but increased in response to urapidil. The accelerated blood flow due to urapidil was counteracted by norepinephrine and norfenefrine. Orciprenaline decreased interstitial glucose concentration and increased nutritive blood flow. The observed changes in blood flow induced by adrenergic agents were not related to glucose uptake.

Discussion: The stimulatory effect of the sympathetic nerves on glucose uptake in subcutaneous adipose tissue appears to be mediated by the alpha1-adrenoceptor. Norepinephrine enhances glucose entry into adipocytes independently of insulin action. In obese subjects with insulin resistance, the alpha1-adrenergic receptor may provide an important alternative pathway for glucose uptake.

MeSH terms

  • Adipocytes / metabolism*
  • Adrenergic alpha-Agonists / pharmacology
  • Adrenergic alpha-Antagonists / pharmacology
  • Adult
  • Female
  • Glucose / metabolism*
  • Humans
  • Insulin Resistance
  • Kinetics
  • Microdialysis
  • Middle Aged
  • Norepinephrine / pharmacology
  • Octopamine / analogs & derivatives
  • Octopamine / pharmacology
  • Piperazines / pharmacology
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / physiology*
  • Sympathetic Nervous System / physiology*

Substances

  • Adrenergic alpha-Agonists
  • Adrenergic alpha-Antagonists
  • Piperazines
  • Receptors, Adrenergic, alpha-1
  • Octopamine
  • urapidil
  • norfenefrine
  • Glucose
  • Norepinephrine