Cmb. Edwards et al., Subcutaneous glucagon-like peptide-I (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects, CLIN SCI, 95(6), 1998, pp. 719-724
1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released p
ostprandially that stimulates insulin secretion, suppresses glucagon secret
ion and delays gastric emptying. The insulinotropic action of GLP-1 is more
potent under hyperglycaemic conditions. Several published stud ies have in
dicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-depe
ndent (Type 2) diabetes mellitus.
2. We investigated whether subcutaneous GLP-1, at a dose shown to im prove
glycaemic control in early Type 2 diabetes, is insulinotropic at normal fas
ting glucose concentrations. A double-blind, randomized, crossover study of
10 healthy subjects injected with GLP-1 or sari ne subcutaneously after a
16 h fast was performed. The effect on cardiovascular parameters was also e
xamined.
3, GLP-1 caused a near 5-fold rise in plasma insulin concentration. After t
reatment with GLP-1, circulating plasma glucose concentrations fell below t
he normal range in all subjects. One subject had symptoms of hypoglycaemia
after GLP-1. A rise in pulse rate was found which correlated with the fall
in plasma glucose concentration. An increase in blood pressure occurred wit
h GLP-1 injection which was seen at the same time as the rise in plasma GLP
-1 concentrations.
4. This study indicates that subcutaneous GLP-1 can override the normal hom
oeostatic mechanism maintaining fasting plasma glucose in man, and is also
associated with an increase in blood pressure.