Neurochemical Research

, Volume 41, Issue 7, pp 1612–1624 | Cite as

The Effects of Insulin-Induced Hypoglycaemia on Tyrosine Hydroxylase Phosphorylation in Rat Brain and Adrenal Gland

  • Manjula Senthilkumaran
  • Michaela E. Johnson
  • Larisa BobrovskayaEmail author
Original Paper


In this study we investigated the effects of insulin-induced hypoglycaemia on tyrosine hydroxylase (TH) protein and TH phosphorylation in the adrenal gland, C1 cell group, locus coeruleus (LC) and midbrain dopaminergic cell groups that are thought to play a role in response to hypoglycaemia and compared the effects of different concentrations of insulin in rats. Insulin (1 and 10 U/kg) treatment caused similar reductions in blood glucose concentration (from 7.5–9 to 2–3 mmol/L); however, plasma adrenaline concentration was increased 20–30 fold in response to 10 U/kg insulin and only 14 fold following 1 U/kg. Time course studies (at 10 U/kg insulin) revealed that in the adrenal gland, Ser31 phosphorylation was increased between 30 and 90 min (4–5 fold), implying that TH was activated to increase catecholamine synthesis in adrenal medulla to replenish the stores. In the brain, Ser19 phosphorylation was limited to certain dopaminergic groups in the midbrain, while Ser31 phosphorylation was increased in most catecholaminergic regions at 60 min (1.3–2 fold), suggesting that Ser31 phosphorylation may be an important mechanism to maintain catecholamine synthesis in the brain. Comparing the effects of 1 and 10 U/kg insulin revealed that Ser31 phosphorylation was increased to similar extent in the adrenal gland and C1 cell group in response to both doses whereas Ser31 and Ser19 phosphorylation were only increased in response to 1 U/kg insulin in LC and in response to 10 U/kg insulin in most midbrain regions. Thus, the adrenal gland and some catecholaminergic brain regions become activated in response to insulin administration and brain catecholamines may be important for initiation of physiological defences against insulin-induced hypoglycaemia.


Hypoglycaemia Tyrosine hydroxylase Catecholamine cell group Adrenal gland 



We thank the Diabetes Australia Research Trust and the University of South Australia (Australia) for supporting this work. MS is a recipient of the University of South Australia Postgraduate Award. MEJ is a recipient of the Australian Postgraduate Award and University of South Australia top up scholarship. We would like to acknowledge the Reid animal facility staff for their help caring for the animals during the trial.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Manjula Senthilkumaran
    • 1
  • Michaela E. Johnson
    • 1
  • Larisa Bobrovskaya
    • 1
    Email author
  1. 1.School of Pharmacy and Medical Sciences, Sansom Institute for Health ResearchUniversity of South AustraliaAdelaideAustralia

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