Acute hypoglycaemia in man
Insulin-induced hypoglycaemia in man provokes an integrated hormonal and metabolic response to restore normoglycaemia. Secretion of counterregulatory hormones promote hepatic glycogenolysis and gluconeogenesis, and mobilise substrates from extra-hepatic tissues. Both adrenergic and cholinergic neural mechanisms are activated by hypoglycaemia, but their contributions to the control of metabolic recovery are not clear. Activation of the sympatho-adrenal system does not appear to be essential for blood glucose recovery. The effect of acute hypoglycaemia on pancreatic beta cell function in response to a subsequent meal was studied in normal subjects. Suppression of endogenous insulin secretion following hypoglycaemia persisted until ingestion of a meal at 210 minutes after insulin injection. After the meal carbohydrate intolerance was associated with an abnormal pattern of insulin secretion, characterised by a delay in the early post-prandial rise of plasma insulin and late hyperinsulinaemia. Investigations of the possible underlying mechanisms implicated glucopenia of the pancreatic beta cells. The contributions of adrenergic and cholinergic mechanisms to metabolic recovery from hypoglycaemia were studied in tetraplegic subjects with a pre-ganglionic sympathectomy (adrenergic denervation), one group of whom were given atropine (combined adrenergic denervation and cholinergic blockade). Blood glucose recovery was impaired only in the tetraplegic subjects given atropine. Both tetraplegic groups demonstrated a reduced blood lactate response, a delayed rise of plasma free fatty acids and an absent cyclic AMP response. Changes in pancreatic glucagon and C-peptide following hypoglycaemia were appropriate to blood glucose values, and were not influenced significantly by islet denervation. Stimulation of glucagon secretion occurred independent of cholinergic vagal control. In the tetraplegic subjects given atropine, the plasma Cortisol response was impaired and the pattern of ACTH secretion was abnormal, suggesting possible blockade of central cholinergic receptors at hypothalamic level. This Cortisol deficiency may explain the delayed blood glucose recovery in these subjects.