Table 1.

Summary of Features and Mechanisms Reviewed

	GLP-1	Amylin
Source	• Intestinal L-cells	• Pancreatic β-cells
	• Neurons in NTS
Receptor and distribution	• Class B GPCR	• Class B GPCR + RAMP
	• Widespread receptor distribution (e.g. islets, brain, heart, kidney, gastrointestinal tract)	• Localized CNS distribution – key receptors in hindbrain AP. Also expressed in nucleus accumbens, dorsal raphe and SFO
β-cell	• Insulinotropic/Amylinotropic	• Co-secreted and co-released with insulin
	• Increased β-cell mass via direct and indirect mechanisms
Glucagon secretion	• Glucagonostatic (with ‘hypoglycaemic’ override)	• Glucagonostatic (with ‘hypoglycaemic’ override)
	• Direct and indirect/paracrine mechanisms reported	• Activation of AP and then vagally transmitted (proposed)
Gastric emptying	• Decreases rate	• Decreases rate
	• Current evidence favours neural reflex triggered by peripheral GLP-1 activating vagal afferents innervating the gut/portal area	• Activation of AP, then transmitted by vagal efferents
Food intake	• Decreases intake	• Decreases intake
	• Central and peripheral mechanisms	• Mediated via direct effects on AP
		• Intact vagus not required
Available knockout models	• Proglucagon peptides (Gcggfp/gfp)	• Amylin deficient mice
	• GLP-1R−/−	• No specific receptor knockouts
	• Double incretin receptor knockout (GLP-1R−/− and GIP-R−/−)	• RAMPS (only) have been deleted or over-expressed
		• Calcitonin receptor knockouts
Future therapeutic approaches in metabolic disease	• Analogueing and improved delivery	• Analogueing and improved delivery
	• Hormonal combinations	• Hormonal combinations (e.g. amylin/leptin synergy evident in preclinical and clinical studies)
	• Allosteric modulators
	• ‘Phybrids’/Chimeras	• ‘Phybrids’/Chimeras
Other disease areas of note	• Neurodegenerative diseases (Parkinson's, Alzheimer's)	• Neuropsychiatric diseases (anxiety, depression)