Amylin is a
peptide hormone which is co-secreted with
insulin from the pancreatic beta-cell. Type 1 diabetic individuals and some Type 2 diabetic individuals are characterised by
amylin deficiency. Animal experiments have revealed several actions of
amylin on intermediary metabolism, of these some have been demonstrated to be of potential physiological relevance in humans. In particular
amylin appears to have important actions in controlling prandial
glucose homeostasis. The
peptide hormone inhibits postprandial
glucagon secretion and delays gastric emptying thereby modifying postprandial hyperglycaemia in diabetic individuals which presumably adds to overall glycaemic control without a concomitant increase in the number of severe hypoglycaemic episodes. Moreover,
amylin acts as a satiety agent.
Amylin replacement may therefore improve glycaemic control in
diabetes mellitus. However, human
amylin exhibits physicochemical properties predisposing the
peptide hormone to aggregate and form
amyloid fibres, which makes it unsuitable for pharmacological use. A stable analogue,
pramlintide, with actions and pharmacokinetic and pharmacodynamic properties similar to the native
peptide has therefore been developed. The efficacy and safety of
pramlintide administration to diabetic individuals have been tested in a large number of clinical trials. It is the aim of this review to describe possible (patho)physiological actions of
amylin as demonstrated in animal and human models, to discuss the background for potential
amylin (analogue) replacement in
diabetes mellitus and to review results from clinical trials with the
amylin receptor analogue
pramlintide.