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Dysfunction in the β2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia

  • Pharmacodynamics
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Abstract

The majority of the impaired symptoms in hypoglycaemia unawareness, such as palpitations, tachycardia and tremor, are caused by increased release of adrenaline (ADR) and noradrenaline (NA), and induced by stimulation of β-adrenergic receptors. Binding of ADR or NA to the β-adrenergic receptor generates a signal, transmitted via a guanine nucleotide binding protein complex (G-protein), which in turn activates adenylate cyclase with increased production of cAMP. The aim of this study was to show whether IDDM-patients with hypoglycaemia unawareness had deficient coupling between β2-adrenergic receptors and G-proteinscompared to IDDM-patients with hypoglycaemia awareness and healthy controls. The IDDM-patients were subgrouped as hypoglycaemia aware or unaware based on questionnaire answers, clinical information and the results of isoprenaline sensitivity tests. Mononuclear leukocytes (MNL) were isolated from venous blood. By saturation binding experiments, using [125I]-(-)-iodopindolol ((-)-IPIN), total receptor number (Bmax) and affinity (Kd) were determined. By displacement experiments the relative number of low-and high-affinity receptors for the β-adrenergic agonist (-)-isoprenaline ((-)-ISO) were determined. We found no difference in Bmax- or Kd-values for (-)-IPIN between the subgroups. However, there was a reduced capability to form high-affinity binding complexes with (-)-ISO in MNL from IDDM-patients with hypoglycaemia unawareness. It was concluded that hypoglycaemia unawareness in IDDM was associated with dysfunction of the proximal β2-adrenergic signal pathway.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Medical Biology, University of Tromsø, N-9037, Tromsø, Norway

    T. S. Trovik, A. Vaartun & G. Sager

  2. Department of Internal Medicine, University Hospital of Tromsø, N-9038, Tromsø, Norway

    R. Jorde

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  1. T. S. Trovik
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  2. A. Vaartun
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  3. G. Sager
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  4. R. Jorde
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Trovik, T.S., Vaartun, A., Sager, G. et al. Dysfunction in the β2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia. Eur J Clin Pharmacol 48, 327–332 (1995). https://doi.org/10.1007/BF00194946

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  • DOI: https://doi.org/10.1007/BF00194946

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