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Arrestin-independent internalization of the GLP-1 receptor is facilitated by a GRK, clathrin, and caveolae-dependent mechanism.
FEBS J
January 2025
Department of Drug Design and Pharmacology, University of Copenhagen, Denmark.
The glucagon-like peptide-1 receptor (GLP-1R) plays an important role in regulating insulin secretion and reducing body weight, making it a prominent target in the treatment of type 2 diabetes and obesity. Extensive research on GLP-1R signaling has provided insights into the connection between receptor function and physiological outcomes, such as the correlation between Gs signaling and insulin secretion, yet the exact mechanisms regulating signaling remain unclear. Here, we explore the internalization pathway of GLP-1R, which is crucial for controlling insulin release and maintaining pancreatic beta-cell function.
View Article and Find Full Text PDFLong-term prognostic impact of glucagon-like peptide-1 receptor agonist before ST-segment elevation myocardial infarction in patients with type 2 diabetes: a nationwide cohort study.
Cardiovasc Diabetol
January 2025
Department of Cardiology, Rigshospitalet, Copenhagen University Hospital, Inge Lehmanns Vej 7, Copenhagen, 2100, Denmark.
Background: Glucagon-like peptide-1 receptor agonist (GLP-1RA) treatment reduces cardiovascular events in type 2 diabetes. Yet, the impact of GLP-1RA treatment before ST-segment elevation myocardial infarction (STEMI) on long-term prognosis in patients with type 2 diabetes remains unclear. In patients with STEMI and type 2 diabetes, we aimed to investigate the association between long-term prognosis and GLP-1RA treatment before STEMI.
View Article and Find Full Text PDFType 2 Diabetes Mellitus Exacerbates Pathological Processes of Parkinson's Disease: Insights from Signaling Pathways Mediated by Insulin Receptors.
Neurosci Bull
January 2025
Center for Translational Neuromedicine and Neurology, School of Life Sciences, Institute for Brain Sciences Research, Henan University, Huaihe Hospital of Henan University, Kaifeng, 475004, China.
Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism.
View Article and Find Full Text PDFDiabetic Kidney Disease.
Dis Mon
January 2025
Division of Nephrology, Texas A&M University College of Medicine in Dallas, Dallas, TX 75246, USA.
Diabetic kidney disease is a leading cause of kidney failure worldwide and is easily detectable with screening examination. Diabetes causes hyperfiltration and activation of the renin-angiotensin aldosterone system by hemodynamic changes within the nephron, which perpetuates damaging physiology. Diagnosis is often clinical after detection of heavy proteinuria in a patient with diabetes,but can be confirmed by observation of histologic stages on kidney biopsy.
View Article and Find Full Text PDFDual GIP and GLP-1 receptor agonist tirzepatide alleviates hepatic steatosis and modulates gut microbiota and bile acid metabolism in diabetic mice.
Int Immunopharmacol
January 2025
Department of Endocrinology, Second Hospital of Shanxi Medical University, Taiyuan 030000, China. Electronic address:
Tirzepatide is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors and is a promising therapeutic option for type 2 diabetes mellitus (T2DM). Nevertheless, its effect and underlying mechanism on hepatic steatosis remain ambiguous. Herein, we explored the impact of tirzepatide on improving hepatic steatosis in diabetic mice, with a particular focus on the gut microbiota and bile acids (BAs) using animal models.
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