Related Experiment Video
Updated: May 21, 2026
09:16
Mixed Primary Cultures of Murine Small Intestine Intended for the Study of Gut Hormone Secretion and Live Cell Imaging of Enteroendocrine Cells
Published on: April 20, 2017
TGR5 potentiates GLP-1 secretion in response to anionic exchange resins
Taoufiq Harach1, Thijs W H Pols, Mitsunori Nomura
1Laboratory of Integrative and Systems Physiology-LISP, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Scientific Reports
|June 6, 2012
Summary
Anionic exchange resins improve glycemic control by enhancing glucagon-like peptide-1 (GLP-1) secretion. This effect is mediated by the TGR5 receptor, particularly in the colon, highlighting a novel therapeutic pathway for diabetes.
Area of Science:
- Metabolic diseases
- Endocrinology
- Pharmacology
Background:
- Anionic exchange resins are known cholesterol-lowering agents.
- These resins may lower blood sugar (glycemia) in diabetic patients.
- Enhanced intestinal glucagon-like peptide-1 (GLP-1) secretion is a proposed mechanism.
Purpose of the Study:
- To investigate the role of anionic exchange resins in GLP-1 secretion and glycemic control.
- To determine the involvement of the TGR5 receptor in these effects.
- To identify the primary site of GLP-1 secretion following resin treatment.
Main Methods:
- Diet-induced animal models of
- diabesity
- were used.
- GLP-1 secretion and glycemic control were measured after resin administration.
- The role of TGR5 was assessed, and GLP-1 production in the colon was investigated.
Main Results:
- Resin exposure significantly enhanced GLP-1 secretion and improved glycemic control.
- These effects were critically dependent on the TGR5 receptor.
- The colon was identified as a major site of resin-induced GLP-1 secretion.
- Resins increased GLP-1 precursor transcript production and local TGR5 agonist levels in the colon.
Conclusions:
- TGR5 is essential for mediating enhanced GLP-1 release induced by anionic exchange resins.
- Anionic exchange resins represent a promising therapeutic strategy for managing diabetes via TGR5 activation and GLP-1 potentiation.
Related Concept Videos
01:24Glucagon-like Receptor Agonists
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by the...
01:23Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists
Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
01:09GPCRs Regulate Adenylyl Cylase Activity
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Two...
01:12GPCR Desensitization
G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
01:06Oral Hypoglycemic Agents: Glinides
Repaglinide (Prandin) and Nateglinide (Starlix), known as glinides, are oral insulin secretagogues that stimulate insulin release from pancreatic β cells by closing the ATP-sensitive potassium channels (KATP channel). Repaglinide controls insulin release from pancreatic β cells by managing potassium efflux. It shares two binding sites with sulfonylureas and also has a unique site, indicating overlapping mechanisms of action. With a rapid onset and a 4-7 hour duration, it effectively manages...
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...