ArticleNature medicine2016
TCF1 links GIPR signaling to the control of beta cell function and survival.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 147 citations in OpenAlex.
- Clinical Potential of GIP in Type 2 Diabetes and Obesity.Diabetes care · 2026Review
- GIP receptor agonism suppresses inflammation-induced aversion and food intake via distinct circuits.Cell reports · 2026Article
- Genome-wide cell type-specific and sex-specific transcriptional dysregulation in the islet of Langerhans underlies islet dysfunction in Down syndrome-related diabetes.bioRxiv : the preprint server for biology · 2026Article
- Glucose-dependent insulinotropic polypeptide (GIP).Trends in endocrinology and metabolism: TEM · 2026Article
- Alternative methods for pharmacological research on the action mechanisms of natural products used in the treatment of type 2 diabetes: a systematic review.Frontiers in pharmacology · 2026Review
- α cells use both PC1/3 and PC2 to process proglucagon peptides and control insulin secretion.Science advances · 2025Article
- Glucose-dependent insulinotropic polypeptide receptor signaling in oligodendrocytes increases the weight-loss action of GLP-1R agonism.Cell metabolism · 2025Article
- GIP receptor agonism suppresses inflammation-induced aversion and food intake via distinct circuits.bioRxiv : the preprint server for biology · 2025Article
- Fluorescent GLP1R/GIPR dual agonist probes reveal cell targets in the pancreas and brain.Nature metabolism · 2025Article
- Review
- GIP Receptor Antagonists in the Pharmacotherapy of Obesity: Physiologic, Genetic, and Clinical Rationale.Diabetes · 2025Review
- Islet hormones at the intersection of glucose and amino acid metabolism.Nature reviews. Endocrinology · 2025Review
- GIPR agonism and antagonism decrease body weight and food intake via different mechanisms in male mice.Nature metabolism · 2025Article
- The Premise of the Paradox: Examining the Evidence That Motivated GIPR Agonist and Antagonist Drug Development Programs.Journal of clinical medicine · 2025Review
- Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice.JCI insight · 2024Article
- Activation of Gs signaling in mouse enteroendocrine K cells greatly improves obesity- and diabetes-related metabolic deficits.The Journal of clinical investigation · 2024Article
- Cross-talk between oxidative stress and lipid metabolism regulators reveals molecular clusters and immunological characterization in polycystic ovarian syndrome.Lipids in health and disease · 2024Article
- Evaluating glucose-dependent insulinotropic polypeptide and glucagon as key regulators of insulin secretion in the pancreatic islet.American journal of physiology. Endocrinology and metabolism · 2024Review
- G Protein-Coupled Receptors: A Century of Research and Discovery.Circulation research · 2024Review
- New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes-Beyond and within GLP-1 Receptor Agonists.Biomedicines · 2024Review
26 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The glucagon-like peptide-1 (GLP-1) receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor transduce nutrient-stimulated signals to control beta cell function. Although the GLP-1 receptor (GLP-1R) is a validated drug target for diabetes, the importance of the GIP receptor (GIPR) for the function of beta cells remains uncertain. We demonstrate that mice with selective ablation of GIPR in beta cells (MIP-Cre:Gipr(Flox/Flox); Gipr(-/-βCell)) exhibit lower levels of meal-stimulated insulin secretion, decreased expansion of adipose tissue mass and preservation of insulin sensitivity when compared to MIP-Cre controls. Beta cells from Gipr(-/-βCell) mice display greater sensitivity to apoptosis and markedly lower islet expression of T cell-specific transcription factor-1 (TCF1, encoded by Tcf7), a protein not previously characterized in beta cells. GIP, but not GLP-1, promotes beta cell Tcf7 expression via a cyclic adenosine monophosphate (cAMP)-independent and extracellular signal-regulated kinase (ERK)-dependent pathway. Tcf7 (in mice) or TCF7 (in humans) levels are lower in islets taken from diabetic mice and in humans with type 2 diabetes; knockdown of TCF7 in human and mouse islets impairs the cytoprotective responsiveness to GIP and enhances the magnitude of apoptotic injury, whereas restoring TCF1 levels in beta cells from Gipr(-/-βCell) mice lowers the number of apoptotic cells compared to that seen in MIP-Cre controls. Tcf7(-/-) mice show impaired insulin secretion, deterioration of glucose tolerance with either aging and/or high-fat feeding and increased sensitivity to beta cell injury relative to wild-type (WT) controls. Hence the GIPR-TCF1 axis represents a potential therapeutic target for preserving both the function and survival of vulnerable, diabetic beta cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.