In the pancreas

• The major source of GLP-1 that binds GLP-1 receptor in the healthy islet is still unresolved, although GLP-1 produced in β-cells may play a more important role in the injured pancreas.
• Direct effects on β-cell function and glucagon secretion in the pancreas remain debated and are unlikely to be mediated by the GLP-1 receptor.

In the brain and nervous system

• Glucagon-like peptides (including GLP-1), and the GLP-1 receptor are widely distributed throughout the central nervous system.
• Neurons in the brainstem produce and use GLP-1 as a neurotransmitter that is stored until release in the axon terminals.
• GLP-1 has an essential role in the control of blood glucose, and is dispensable for the suppression of food intake; GLP-1-producing PPG neurons are activated by signals linked to short- and long-term energy balance, but do not seem to play a major role in determining body weight.

In the cardiovascular system

• Cardiovascular safety trials with GLP-1RA have demonstrated reduction in all-cause and cardiovascular mortality, and lower rates of major cardiovascular events, including stroke and myocardial infarction.
• GLP-1RA also increase heart rate in humans and animals, in part due to activation of the sympathetic nervous system, and inhibition of the parasympathetic nervous system.
• Despite considerable research, the identity of GLP-1 receptor cells in the heart remains elusive.