Elevated fetuin-A levels, chemokines and islet-resident macrophages are crucial factors associated with obesity-mediated type 2 diabetes (T2D). Here, the aim of the study was to investigate the effect of MIN6 (a mouse insulinoma cell line)-derived fetuin-A (also known as AHSG) in macrophage polarization and decipher the effect of M1 type pro-inflammatory macrophages in commanding over insulin secretion. MIN6 and islet-derived fetuin-A induced expression of the M1 type macrophage markers Emr1 (also known as Adgre1), Cd68 and CD11c (Itgax) (∼1.8 fold) along with increased cytokine secretion. Interestingly, suppression of fetuin-A in MIN6 successfully reduced M1 markers by ∼1.5 fold. MIN6-derived fetuin-A also induced chemotaxis of macrophages in a Boyden chamber chemotaxis assay. Furthermore, high-fat feeding in mice showed elevated cytokine and fetuin-A content in serum and islets, and also migration and polarization of macrophages to the islets, while β-cells failed to meet the increased insulin demand. Moreover, in MIN6 culture, M1 macrophages sharply decreased insulin secretion by ∼2.8 fold. Altogether our results support an association of fetuin-A with islet inflammation and β-cell dysfunction, owing to its role as a key chemoattractant and macrophage polarizing factor.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1242/jcs.258507 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
A Comprehensive Analysis of Diabetic Complications and Advances in Management Strategies.
J Atheroscler Thromb
January 2025
Department of Endocrinology and Metabolism, Institute of Medicine, University of Tsukuba.
Diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), is a pervasive chronic disease that affects millions of people worldwide. It predisposes individuals to a range of severe microvascular and macrovascular complications, which drastically impact the patient's quality of life and increase mortality rates owing to various comorbidities. This extensive review explores the intricate pathophysiology underlying diabetic complications, focusing on key mechanisms, such as atherosclerosis, insulin resistance, chronic inflammation, and endothelial dysfunction.
View Article and Find Full Text PDFThree-Year Follow-up After Antiviral Treatment in New-Onset Type 1 Diabetes: Results From the Diabetes Virus Detection and Intervention Trial.
Diabetes Care
January 2025
Division of Pediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway.
Objective: In the Diabetes Virus Detection and Intervention trial, antiviral treatment with pleconaril and ribavirin decreased the decline, compared with placebo, in endogenous C-peptide 1 year after diagnosis of type 1 diabetes (T1D) in children and adolescents. This article reports the results 2 and 3 years after diagnosis.
Research Design And Methods: This was a multicenter, randomized, placebo-controlled (1:1) trial of 96 children and adolescents aged 6-15.
A comparative analysis of current С-peptide assays compared to a reference method: can we overcome inertia to standardization?
Clin Chem Lab Med
January 2025
Pathology & Anatomical Sciences, University of Missouri, Columbia MO, USA.
Objectives: C-peptide is an equimolar by-product of insulin biosynthesis. It is used clinically to assess insulin secretion and differentiate types of diabetes. However, the lack of standardization across assays limits its broader application.
View Article and Find Full Text PDFUltrafast multicellular calcium imaging of calcium spikes in mouse beta cells in tissue slices.
Acta Physiol (Oxf)
February 2025
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Background: The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.
View Article and Find Full Text PDFBeta cell function and global glucose metabolism are impaired in Dp(16)1Yey mouse model of Down syndrome.
Diabetes Obes Metab
January 2025
BFA, UMR 8251, CNRS, Team « Biologie et Pathologie du Pancréas Endocrine », Université Paris Cité, Paris, France.
Aims: Down syndrome (DS) or trisomy 21 is the most prevalent genetic disorder in the world. In addition to common symptoms such as intellectual disabilities and morphological abnormalities, several comorbidities are associated with DS, including metabolic dysfunction. Obesity and diabetes are more prevalent in people with DS compared with the general population.
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!