Blood sugar control

The physiological control of blood glucose is complex. While the major role belongs to insulin, a multitude of other hormonal influences apply. It should also be remembered that insulin has other actions beyond the regulation of blood glucose. Pharmacological control of blood glucose becomes necessary in situations of elevation and depression of blood glucose beyond the homeostatic limits, in other words due to hyperglycaemia or hypoglycaemia. The causes of failure in regulation of blood glucose are given in Figure EP1.

Treatment of hypoglycaemia is directed towards administration of glucose and removal of the root cause. Treatment of hyperglycaemia includes removal of the cause, administration of insulin in the acute phase and at a later stage augmentation of both the secretion and effect of endogenous insulin.

Insulin receptor

The insulin receptor is a complex of four glycoprotein subunits (ααββ) linked by disulphide bridges to form a cylinder. The α units are entirely extracellular and contain the insulin binding site. The β subunit spans the cell membrane, and the intracellular part has tyrosine kinase activity. The α subunit has a repressive effect on this activity that is removed by the conformational change resulting from insulin binding. The tyrosine kinase acts on insulin receptor substrate 1 (IRS-1), triggering a chain of action culminating in the activation of glycogen synthetase, phosphorylase kinase and glycogen phosphorylase. IRS-1 is also a substrate for insulin-like growth factor 1 (IGF-1) receptors.