GLP-1 and GIP receptor signaling in beta cells – A review of receptor interactions and co-stimulation

The Location of Missense Variants in the Human GIP Gene Is Indicative for Natural Selection

“…In the N-terminal segment (1-15), positions (1,3,5,8-11, and 15) displayed a high degree of conservation across species (Figure 4A). In the core segment (16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30), the hydrophobic positions 22,23,26, and 27, complementing a binding groove in the GIPR (57), showed the highest degree of conservation (CS < -1.328). The C-terminal segment (31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41)(42) represents the C-terminal tail, which is unique for GIP(1-42) and structurally less ordered than the closely related class B1 peptides (58).…”

“…GIP(1-42) appears to signal through a single receptor, the GIPR, which is a Gα s coupled receptor, activating adenylyl cyclase, resulting in generation of cAMP with subsequent downstream signaling ( 30 , 31 ). Moreover, the GIPR has been shown to also signal through Gα i and Gα q to some extent ( 32 , 33 ).…”

Gut physiology meets microbiome science

“…Ghrelin secretion from stomach is simultaneously inhibited by the incoming food and together with secretin and CCK those three hormones are important for short-time satiety effects in brain. In addition to GLP-1 secreted from L-cells, gastric insulinotropic peptide (GIP) secreted from K-cells affects the postprandial glucose profiles in systemic circulation as well as insulin output from the endocrine pancreas (Gasbjerg et al, 2019; Mayendraraj et al, 2022).…”

The catcher in the gut: Tirzepatide, a dual incretin analog for the treatment of type 2 diabetes mellitus and obesity

“…1 [ 38 , 39 , 41 ]. Both GLP-1 and GIP present important insulin secreting actions and beneficial effects on beta cells proliferation and survival [ 42 ]. GLP-1 has satiety-promoting and anorexigenic properties, influencing food reward networks and the motivational drive for overeating.…”

“…GLP-1 appears to exert actions beyond the metabolic regulation as its receptors found in the cardiovascular system imply direct cardioprotective effects, apart from the indirect effects through weight loss and glycemic control [ 44 ]. GIP appears to add on the effects of GLP-1 on the pancreas increasing glucagon and somatostatin secretion, which is potentially beneficial against the hypoglycemic effects of insulin alone [ 41 , 42 ]. Of importance, GIP is linked to increased adipose tissue blood flow (ATBF) postprandially, which is usually blunted in individuals with obesity and/or T2DM, and potentially contributes to ectopic fat deposition linked to insulin resistance [ 12 , 21 , 41 ].…”