Diabetes Mellitus — A Membrane Receptor Defect

Summary: It is proposed that diabetes mellitus, characterised by hyperglycaemia and either relative or absolute insulin deficiency, represents a spectrum of clinical disorders produced by one or more abnormalities at hormone or glucose receptor sites in the membrane of the pancreatic islet beta cell. Separate receptors with finite binding affinity have been described for glucose, glucagon, gastrointestinal hormones and adrenaline. In diabetes mellitus glucose‐receptor binding is always abnormal. In some diabetics, one or more of the hormone‐receptor binding sites may be abnormal in addition. Sulphonylureas such as tolbutamide, act by either altering the properties of the hormone‐receptor binding site or modifying the tertiary structure of the insulinogenic substance to provide tighter or more effective binding—they lubricate the lock. Diabetes mellitus may represent a spectrum of disorders presenting with the same clinical features. The concept of selective receptor involvement may clarify the confusion surrounding the mode of inheritance of the disorder and pro‐vide a rational basis for early diagnosis and effective management.