Oral Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

Adrenaline and the Glucose Counterregulatory Response: An Orexinergic Connection (#161)

Tony J Verberne 1 , W S Korim 1
  1. Department of Medicine, University of Melbourne, Austin Health, Heidelberg, VIC, Australia

The glucose counterregulatory response helps restore normoglycaemia in response to hypoglycaemia or neuroglucoprivation. In diabetes, adrenaline is the major counterregulatory hormone since diabetic patients also lose the ability to secrete glucagon. It has been assumed that sympathetic control of adrenaline secretion operates similarly to sympathetic vasomotor control. However, we have shown that adrenal presympathetic neurons in the rostral ventrolateral medulla (RVLM) that control adrenaline secretion are a unique population that are activated during glucoprivation. Local neuroglucoprivation in the perifornical hypothalamic area (PeH) activates adrenal sympathetic nerve activity (ASNA) through activation of orexin receptors in the RVLM. In addition, inhibition of PeH neurons with muscimol abolishes the increase in ASNA produced by systemic glucoprivation. These findings suggest that declining brain glucose is sensed by neurons in, or close to the PeH and elicits a counterregulatory response. Conversely, local glucoprivation in RVLM does not activate ASNA, suggesting that sympathoadrenal premotor neurons are not intrinsically glucose-sensitive. PeH neurons with projections to the RVLM are activated during insulin-induced hypoglycaemia suggesting that these neurons are integral to the glucose counterregulatory response. These findings indicate that orexin inputs to adrenal medullary presympathetic neurons in the RVLM mediate adrenaline release in response to neuroglucoprivation or hypoglycaemia.