Altered Gi signaling in enteroendocrine K cells in vivo causes pronounced changes in glucose homeostasis
Abstract
Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that promotes postprandial insulin release and euglycemia. Although GIP is the dominant incretin in humans, the precise mechanisms regulating GIP release from enteroendocrine K cells in vivo remain to be elucidated. Heterotrimeric G proteins of the Gi family regulate numerous key physiological functions. To explore the potential role of these proteins in modulating K cell function in vivo, we analyzed mutant mice that allowed us to selectively stimulate Gi signaling in K cells or studied mice lacking functional Gi in K cells only. Stimulation of K cell Gi signaling in vivo and in vitro led to reduced GIP release via an exchange protein directly activated by 3'-5'-cyclic adenosine monophosphate 2-dependent pathway and various metabolic deficits. In contrast, inactivation of this class of G proteins in K cells caused elevated plasma GIP levels and pronounced improvements in glucose homeostasis in lean and obese mice. These data provide important insights into the mechanisms of GIP release.
Read the paper
Related studies
- eggNOG 5.0: a hierarchical, functionally and phylogenetically annotated orthology resource based on 5090 organisms and 2502 viruses
- Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer
- OptiType: precision HLA typing from next-generation sequencing data
- Nicotinic Cholinergic System and COVID-19: In Silico Identification of an Interaction between SARS-CoV-2 and Nicotinic Receptors with Potential Therapeutic Targeting Implications
- Saccharomyces cerevisiae cells have three Omega class glutathione S-transferases acting as 1-Cys thiol transferases
- Hemolysis at low blood flow rates: in-vitro and in-silico evaluation of a centrifugal blood pump
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.