ArticleMolecular and cellular biology2008
Glucose-dependent insulinotropic polypeptide-mediated up-regulation of beta-cell antiapoptotic Bcl-2 gene expression is coordinated by cyclic AMP (cAMP) response element binding protein (CREB) and cAMP-responsive CREB coactivator 2.
Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 136 citations in OpenAlex.
- Sitagliptin Treatment After Total Pancreatectomy With Islet Autotransplantation: A Randomized, Placebo-Controlled Study.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2017Trial
- Modulation of the tumor microenvironment by incretins and glucagon: Metabolic and immune mechanisms (Review).Experimental and therapeutic medicine · 2026Review
- The role of GIP in carbohydrate metabolism: Implications in the development of therapies for T2DM, a narrative review.Histology and histopathology · 2026Review
- Positive inotropic effects of glucose-dependent insulinotropic polypeptide in the human atrium and the mouse atrium.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Glucose-Dependent Insulinotropic Polypeptide in Incretin Physiology: Role in Health and Disease.Endocrine reviews · 2025Review
- Physiology and clinical applications of GIP.Endocrine journal · 2025Review
- Autophagy induced by metabolic processes leads to solid tumor cell metastatic dormancy and recurrence.Medical oncology (Northwood, London, England) · 2025Review
- GLP-1 and GIP agonism has no direct actions in human hepatocytes or hepatic stellate cells.Cellular and molecular life sciences : CMLS · 2024Article
- Tirzepatide, GIP(1-42) and GIP(1-30) display unique signaling profiles at two common GIP receptor variants, E354 and Q354.Frontiers in pharmacology · 2024Article
- Metabolic Adaptions/Reprogramming in Islet Beta-Cells in Response to Physiological Stimulators-What Are the Consequences.Antioxidants (Basel, Switzerland) · 2022Review
- What turns CREB on? And off? And why does it matter?Cellular and molecular life sciences : CMLS · 2020Review
- Secretin Prevents Apoptosis in the Developing Cerebellum Through Bcl-2 and Bcl-xL.Journal of molecular neuroscience : MN · 2019Article
- Adaptive Transcriptional Responses by CRTC Coactivators in Cancer.Trends in cancer · 2019Review
- Inhibition of TBK1/IKKε Promotes Regeneration of Pancreatic β-cells.Scientific reports · 2018Article
- GDC-0879, a BRAFCell chemical biology · 2018Article
- Genetically engineered pigs as models for human disease.Disease models & mechanisms · 2018Review
- Article
- Optogenetic regulation of insulin secretion in pancreatic β-cells.Scientific reports · 2017Article
- TNFα-induced DLK activation contributes to apoptosis in the beta-cell line HIT.Naunyn-Schmiedeberg's archives of pharmacology · 2017Article
- Role of GIP receptor signaling in β-cell survival.Diabetology international · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic AMP (cAMP)/protein kinase A (PKA) cascade plays a central role in beta-cell proliferation and apoptosis. Here, we show that the incretin hormone glucose-dependent insulinotropic polypeptide (GIP) stimulates expression of the antiapoptotic Bcl-2 gene in pancreatic beta cells through a pathway involving AMP-activated protein kinase (AMPK), cAMP-responsive CREB coactivator 2 (TORC2), and cAMP response element binding protein (CREB). Stimulation of beta-INS-1 (clone 832/13) cells with GIP resulted in increased Bcl-2 promoter activity. Analysis of the rat Bcl-2 promoter revealed two potential cAMP response elements, one of which (CRE-I [GTGACGTAC]) was shown, using mutagenesis and deletion analysis, to be functional. Subsequent studies established that GIP increased the nuclear localization of TORC2 and phosphorylation of CREB serine 133 through a pathway involving PKA activation and reduced AMPK phosphorylation. At the nuclear level, phospho-CREB and TORC2 were demonstrated to bind to CRE-I of the Bcl-2 promoter, and GIP treatment resulted in increases in their interaction. Furthermore, GIP-mediated cytoprotection was partially reversed by small interfering RNA-mediated reduction in BCL-2 or TORC2/CREB or by pharmacological activation of AMPK. The antiapoptotic effect of GIP in beta cells is therefore partially mediated through a novel mode of transcriptional regulation of Bcl-2 involving cAMP/PKA/AMPK-dependent regulation of CREB/TORC2 activity.
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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.