Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
Author:
Arely Reséndiz-Jiménez1, Cristian Arbez-Evangelista1, Omar Arroyo-Xochihua1, Antonio Palma-Jacinto José2, Isela Santiago-Roque2, Yeimy Mar De León-Ramírez3ORCID, Xcaret Alexa Hernández-Domínguez3, Omar Arroyo-Helguera3
Affiliation:
1. Centro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa 91190, Veracruz, Mexico 2. Laboratory of Biochemistry and Neurotoxicology, Faculty of Bioanalysis-Xalapa, Universidad Veracruzana, Médicos y Odontólogos S/N, Unidad del Bosque, Xalapa 91190, Veracruz, Mexico 3. Laboratorio de Biomedicina y Salud Pública, Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Animas, Xalapa 91190, Veracruz, Mexico
Abstract
Background: Epidemiological clinical reports have shown an association between iodine excess with diabetes mellitus type 2 and higher blood glucose. However, the relationship between iodine, the pancreas, adipose tissue, and glucose transport is unclear. The goal of this study was to analyze the effect of iodine concentrations (in Lugol solution) on glucose transport, insulin secretion, and its cytotoxic effects in mature 3T3-L1 adipocytes and pancreatic beta-TC-6 cells. Methods: Fibroblast 3T3-L1, mature adipocytes, and pancreatic beta-TC-6 cells were treated with 1 to 1000 µM of Lugol (molecular iodine dissolved in potassium iodide) for 30 min to 24 h for an MTT proliferation assay. Then, glucose uptake was measured with the fluorescent analog 2-NBDG, insulin receptor, Akt protein, p-Akt (ser-473), PPAR-gamma, and Glut4 by immunoblot; furthermore, insulin, alpha-amylase, oxidative stress, and caspase-3 activation were measured by colorimetric methods and the expression of markers of the apoptotic pathway at the RNAm level by real-time PCR. Results: Low concentrations of Lugol significantly induce insulin secretion and glucose uptake in pancreatic beta-TC-6 cells, and in adipose cells, iodine-induced glucose uptake depends on the serine-473 phosphorylation of Akt (p-Akt) and Glut4. Higher doses of Lugol lead to cell growth inhibition, oxidative stress, and cellular apoptosis dependent on PPAR-gamma, Bax mRNA expression, and caspase-3 activation in pancreatic beta-TC-6 cells. Conclusions: Iodine could influence glucose metabolism in mature adipocytes and insulin secretion in pancreatic beta cells, but excessive levels may cause cytotoxic damage to pancreatic beta cells.
Funder
Public Health Institute Biomedical Research Center CONACyT Dirección General de Investigaciones de la Universidad Veracruzana
Subject
General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology
Reference34 articles.
1. Sapra, A., and Bhandari, P. (2023, November 13). Diabetes Mellitus, StatPearls, Available online: https://www.ncbi.nlm.nih.gov/books/NBK551501/. 2. Diabetes mellitus: The epidemic of the century;Kharroubi;World J. Diabetes,2015 3. Rosiglitazone improves downstream insulin receptor signaling in type 2 diabetic patients;Miyazaki;Diabetes,2003 4. Muscle and adipose tissue insulin resistance: Malady without mechanism?;Fazakerley;J. Lipid Res.,2019 5. IRS1-independent defects define major nodes of insulin resistance;Hoehn;Cell Metab.,2008
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