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Mechanisms underlying glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 secretion.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Gribble, Fiona M 

Abstract

The incretin hormones, glucose-dependent insulinotropic peptide and glucagon-like peptide-1, are secreted from intestinal K- and L cells, respectively, with the former being most abundant in the proximal small intestine, whereas the latter increase in number towards the distal gut. Although an overlap between K- and L cells can be observed immunohistochemically or in murine models expressing fluorescent markers under the control of the two hormone promoters, the majority (>80%) of labeled cells seems to produce only one of these hormones. Transcriptomic analysis showed a close relationship between small intestinal K- and L cells, and glucose sensing mechanisms appear similar in both cell types with a predominant role of electrogenic glucose uptake through sodium-coupled glucose transporter 1. Similarly, both cell types produce the long-chain fatty acid sensing G-protein-coupled receptors, FFAR1 (GPR40) and FFAR4 (GPR120), but differ in the expression/functionality of other lipid sensing receptors. GPR119 and FFAR2/3, for example, have clearly documented roles in glucagon-like peptide-1 secretion, whereas agonists for the endocannabinoid receptor type 1 have been found to show largely selective inhibition of glucose-dependent insulinotropic peptide secretion. In conclusion, although K- and L cell populations overlap and share key molecular nutrient-sensing mechanisms, subtle differences between the responsiveness of the different cell types might be exploited to differentially modulate glucose-dependent insulinotropic peptide or glucagon-like peptide-1 secretion.

Description

Keywords

Gastric inhibitory polypeptide/glucose‐dependent insulinotropic peptide, Glucagon‐like peptide‐1, Secretion, Animals, Enteroendocrine Cells, Gastric Inhibitory Polypeptide, Glucagon-Like Peptide 1, Glucose, Humans, Incretins, Receptors, Cell Surface, Receptors, G-Protein-Coupled

Journal Title

J Diabetes Investig

Conference Name

Journal ISSN

2040-1116
2040-1124

Volume Title

7 Suppl 1

Publisher

Wiley
Sponsorship
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MC_PC_12012)