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ICV GLP-1 reduces food intake in rodents, and this effect is blocked with Exendin ( Glucagon is typically stimulated by the fall in insulin during fasting in concert with low glucose levels, and responds to hypoglycaemia by mobilising hepatic glucose through the stimulation of glycogenolysis and gluconeogenesis ( Fgf21 -/- knock-out mice are protected from these effects ( Given the pre-existing data on GLP-1 and glucagon, we designed a double-blinded randomised cross-over study, in which we gave volunteers who were overweight short-term intravenous infusions of glucagon (50 ng/kg/min or 14 pmol/kg/min), GLP-1 (0.8 pmol/kg/min), combination of glucagon + GLP-1 at the same doses, or placebo over 45 minutes, and demonstrated that there was a significant increase in resting energy expenditure with glucagon alone which was preserved with the combination of glucagon + GLP-1, whereas GLP-1 did not affect energy expenditure ( Pre-Clinical Studies of Synthetic GLP-1/Glucagon Co-Agonists Concurrent to research investigating combination treatments with individual GLP-1 and glucagon infusions, efforts were also focused on optimising the peptide chemistry of native oxyntomodulin, glucagon or GLP-1 in view of designing receptor potent and long-acting synthetic GLP-1/GCG co-agonists

Studies on obese diabetic (ob/ob) mice showed that GIP (Lys16PAL) and GIP (Lys37PAL) long-acting analogs for GIPR increased the insulin response to glucose and improved glucose tolerance [58]

Laboratory studies may focus on its amino acid sequence, molecular identity, receptor interactions and behaviour under controlled experimental conditions

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