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Targeting central pathway of Glucose-Dependent Insulinotropic Polypeptide, Glucagon and Glucagon-like Peptide-1 for metabolic regulation in obesity and type 2 diabetes.
Diabetes Obes Metab
December 2024
Department of Endocrinology, Shanghai Pudong Hospital, Fudan University, Shanghai, China.
Article Synopsis
- Obesity and type 2 diabetes pose major public health issues that affect global health significantly.
- The focus of effective treatments is shifting toward the central nervous system and how it regulates metabolism, especially using incretin-based medications.
- This review aims to summarize the latest research on the neural pathways related to key receptors involved in metabolic control, specifically glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon.
Effect of acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, and estrus phase on cue- and drug-induced fentanyl seeking in female rats.
Behav Pharmacol
February 2025
Department of Neural and Behavioral Sciences.
Opioid use disorder (OUD) is a crisis in the USA. Despite advances with medications for OUD, overdose deaths have continued to rise and are largely driven by fentanyl. We have previously found that male rats readily self-administer fentanyl, with evident individual differences in fentanyl taking, seeking, and reinstatement behaviors.
View Article and Find Full Text PDFPrediction of metabolic subphenotypes of type 2 diabetes via continuous glucose monitoring and machine learning.
Nat Biomed Eng
December 2024
Department of Genetics, Stanford University, Stanford, CA, USA.
The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them).
View Article and Find Full Text PDFPredicting responsiveness to GLP-1 pathway drugs using real-world data.
BMC Endocr Disord
December 2024
Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.
Background: Medications targeting the glucagon-like peptide-1 (GLP-1) pathway are an important therapeutic class currently used for the treatment of Type 2 diabetes (T2D). However, there is not enough known about which subgroups of patients would receive the most benefit from these medications.
Objective: The goal of this study was to develop a predictive model for patient responsiveness to medications, here collectively called GLP-1 M, that include GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors (that normally degrade endogenously-produced GLP-1).
Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH).
Nat Rev Drug Discov
November 2024
Section of Digestive Diseases, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its severe subgroup metabolic dysfunction-associated steatohepatitis (MASH) have become a global epidemic and are driven by chronic overnutrition and multiple genetic susceptibility factors. The physiological outcomes include hepatocyte death, liver inflammation and cirrhosis. The first therapeutic for MASLD and MASH, resmetirom, has recently been approved for clinical use and has energized this therapeutic space.
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