Incretin hormones and obesity DOI Creative Commons
Constanza Alcaino, Frank Reimann, Fiona M. Gribble

et al.

The Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract The incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) play critical roles in co‐ordinating postprandial metabolism, including modulation of insulin secretion food intake. They are secreted from enteroendocrine cells the intestinal epithelium following ingestion, act at multiple target sites pancreatic islets brain. With recent development agonists targeting GLP‐1 GIP receptors for treatment type 2 diabetes obesity, ongoing new incretin‐based drugs with improved efficacy, there is great interest understanding physiology pharmacology these hormones. image

Language: Английский

Understanding the release mechanisms and secretion patterns for glucagon-like peptide-1 using the isolated perfused intestine as a model DOI Creative Commons
Katrine D. Galsgaard, Ida M. Modvig, Jens J. Holst

et al.

Biochemical Society Transactions, Journal Year: 2025, Volume and Issue: 53(01)

Published: Jan. 31, 2025

In the gastrointestinal (GI) tract, food is digested and absorbed while GI hormones are secreted from enteroendocrine cells (EECs). These regulate intake, glucose homeostasis, digestion, motility, metabolism. Although ECCs may express more than a single hormone, usually secrete only one or few hormones. The pattern of EEC secretion varies along length tract as different types scattered in densities tract. Following bariatric surgery, postprandial hypersecretion certain occurs which contributes to postsurgery weight loss. Mimicking this by targeting endogenous secretion, using specific modulators receptors, ion channels, transporters found on EECs, induce loss current research aim. To achieve this, complete understanding release mechanisms, expression transporters, ECC needed. Using vascularly perfused intestinal model, it possible obtain detailed knowledge these mechanisms evaluating effects blocking stimulating well nutrient handling absorption each sections intestine. This mini-review will focus how isolated intestine has been used our group model investigate nutrient-induced with glucagon-like peptide-1 secreting cells.

Language: Английский

Citations

0

Cholecystokinin in intestinal and extraintestinal endocrine cells DOI
Marta Santos-Hernández, Frank Reimann, Fiona M. Gribble

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 87 - 99

Published: Jan. 1, 2025

Language: Английский

Citations

0

Molecular mechanisms of stimulus detection and secretion in enteroendocrine cells DOI Creative Commons

Adam Davison,

Frank Reimann, Fiona M. Gribble

et al.

Current Opinion in Neurobiology, Journal Year: 2025, Volume and Issue: 92, P. 103045 - 103045

Published: May 15, 2025

Language: Английский

Citations

0

Fetal programming by the maternal microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus DOI Creative Commons
Kevin L. Gustafson, Susheel Bhanu Busi, Zachary L. McAdams

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 12, 2024

The microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as gut microbiome, affect numerous host behaviors dependent on central nervous system (CNS). Studies comparing germ-free mice normally colonized have demonstrated influences microbiome anxiety-related behaviors, voluntary activity, and gene expression in CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence maternal neurodevelopment offspring behavior later life. There limited experimental however directly linking long-term neurodevelopmental outcomes, or knowledge regarding mechanisms responsible for such effects.

Language: Английский

Citations

1

Single‐cell transcriptomics of human organoid‐derived enteroendocrine cell populations from the small intestine DOI Creative Commons
Christopher A. Smith, Van B. Lu, Rula Bany Bakar

et al.

The Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 5, 2024

Abstract Gut hormones control intestinal function, metabolism and appetite, have been harnessed therapeutically to treat type 2 diabetes obesity. Our understanding of the enteroendocrine axis arises largely from animal studies, but organoid models make it possible identify, genetically modify purify human cells (EECs). This study aimed map EECs using single‐cell RNA sequencing. Organoids derived duodenum ileum were modified CRISPR‐Cas9 express fluorescent protein Venus driven by chromogranin‐A promoter. Fluorescent CHGA‐Venus organoids purified flow cytometry analysed 10X Cluster analysis separated EEC populations, allowing an examination differentially expressed hormones, nutrient‐sensing machinery, transcription factors exocytotic machinery. Bile acid receptor GPBAR1 was most highly in L‐cells (producing glucagon‐like peptide 1 YY), long‐chain fatty FFAR1 highest I‐cells (cholecystokinin), K‐cells (glucose‐dependent insulinotropic polypeptide) L‐cells, short‐chain FFAR2 ileal enterochromaffin cells, olfactory OR51E1 notably glucose‐sensing sodium glucose cotransporter SLC5A1 K‐ reflecting their known responsiveness ingested glucose. The atlas merged with published data intestine organoids, good overlap between datasets. Understanding similarities differences types will facilitate development drugs targeting for treatment conditions such as diabetes, obesity disorders. image Key points regulate nutrient homeostasis form basis new classes diabetes. As (EECs) comprise only ∼1% epithelium, they are under‐represented current atlases. To compare characterise we generated labelled duodenal biopsies CRISPR‐Cas9. positive sequencing, revealing predominant cell clusters producing different gut hormones. Cell exhibited differential expression machinery including bile receptors, long‐ receptors transporters. Organoid‐derived mapped well onto native extending coverage EECs.

Language: Английский

Citations

1

Incretin hormones and obesity DOI Creative Commons
Constanza Alcaino, Frank Reimann, Fiona M. Gribble

et al.

The Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 22, 2024

Abstract The incretin hormones glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) play critical roles in co‐ordinating postprandial metabolism, including modulation of insulin secretion food intake. They are secreted from enteroendocrine cells the intestinal epithelium following ingestion, act at multiple target sites pancreatic islets brain. With recent development agonists targeting GLP‐1 GIP receptors for treatment type 2 diabetes obesity, ongoing new incretin‐based drugs with improved efficacy, there is great interest understanding physiology pharmacology these hormones. image

Language: Английский

Citations

0