AI Article Synopsis
- GIP (glucose-dependent insulinotropic peptide) plays a crucial role in regulating insulin secretion and glucose metabolism, but its effects on human adipose tissue, especially in obesity and insulin resistance, are still unclear.
- Research demonstrated that GIP receptor (GIPR) expression is lower in adipose tissue from obese individuals and is linked to various metabolic factors, including body mass index and triglyceride levels.
- GIP shows potential as an insulin sensitizer in lean human fat cells, enhancing insulin action and GIPR expression, but these benefits are diminished in obese fat cells due to reduced GIPR levels.
Article Abstract
Context: Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear.
Objective: Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance.
Design: GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients.
Results: GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR.
Conclusions: GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1210/jc.2013-3350 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Molecular pathological characteristics and mechanisms of the liver in metabolic disease-susceptible transgenic pigs.
Life Sci
December 2024
State Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing 100193, China. Electronic address:
Aims: This study aimed to explore the molecular pathological mechanisms of the liver in metabolic disease-susceptible transgenic pigs via multiomics analysis.
Materials And Methods: The triple-transgenic (PNPLA3-GIPR-hIAPP) pig model (TG pig) was successfully constructed in our laboratory via the CRISPR/Cas9 technique previously described. Wild-type (WT) pigs and TG pigs after 2 or 12 months of high-fat and high-sucrose diet (HFHSD) induction (WT2, TG2, WT12, and TG12 groups, respectively) were used as materials.
Glucose-dependent insulinotropic polypeptide receptor signaling alleviates gut inflammation in mice.
JCI Insight
December 2024
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, University of Toronto, Toronto, Canada.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are gut-derived peptide hormones that potentiate glucose-dependent insulin secretion. The clinical development of GIP receptor (GIPR)-GLP-1 receptor (GLP-1R) multi-agonists exemplified by tirzepatide and emerging GIPR antagonist-GLP-1R agonist therapeutics such as maritide is increasing interest in the extra-pancreatic actions of incretin therapies. Both GLP-1 and GIP modulate inflammation, with GLP-1 also acting locally to alleviate gut inflammation in part through anti-inflammatory actions on GLP-1R+ intestinal intraepithelial lymphocytes.
View Article and Find Full Text PDFGLP-1R/NPY2R regulate gene expression, ovarian and adrenal morphology in HFD mice.
J Endocrinol
December 2024
R Moffett, School of Biomedical Sciences, University of Ulster, Coleraine, United Kingdom of Great Britain and Northern Ireland.
Glucagon-like peptide-1 receptor (GLP-1R) and neuropeptide Y receptors (NPYRs) are expressed in reproductive tissues contributing to the regulation of gonadal function. This exploratory study examines the potential impact of their modulation by assessing effects of exendin-4 (Ex-4) and peptide YY (PYY) (3-36) on endocrine ovaries and adrenals, in high-fat diet (HFD) mice. Ex-4 and PYY(3-36) reduced blood glucose and energy intake, with no effects on body weight.
View Article and Find Full Text PDFTreatment with sitagliptin exacerbates the M2 phenotype in macrophages in vitro.
Int Immunopharmacol
January 2025
Mucosal Health and Immunology Laboratory (MHIL), Center for Natural and Human Science, Federal University of ABC, Santo André, São Paulo, Brazil; Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, Brazil. Electronic address:
Article Synopsis
- Macrophages play a crucial role in regulating the immune response both in normal conditions and during inflammation, and sitagliptin, a diabetes drug, has shown potential anti-inflammatory effects.
- This study investigated how sitagliptin affects macrophage polarization, finding that it enhances the M2 macrophage phenotype while reducing pro-inflammatory markers like TNF-α.
- Additionally, sitagliptin treatment impacted mitochondrial function in M2 macrophages, leading to lower energy production and reduced ability to engulf particles.
Red and far-red cleavable fluorescent dyes for self-labelling enzyme protein tagging and interrogation of GPCR co-internalization.
RSC Chem Biol
November 2024
Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP) Berlin 13125 Germany
Post-labelling cleavable substrates for self-labelling protein tags, such as SNAP- and Halo-tags, can be used to study cell surface receptor trafficking events by stripping dyes from non-internalized protein pools. Since the complexity of receptor biology requires the use of multiple and orthogonal approaches to simultaneously probe multiple receptor pools, we report the development of four membrane impermeable probes that covalently bind to either the SNAP- or the Halo-tag in the red to far-red range. These molecules bear a disulfide bond to release the non-internalized probe using the reducing agent sodium 2-mercaptoethane sulfonate (MESNA).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!