Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells

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 eff...

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Main Authors: Reséndiz-Jiménez Arely, Arbez-Evangelista Cristian, Arroyo-Xochihua Omar, Palma-Jacinto José Antonio, Santiago-Roque Isela, De León-Ramírez Yeimy Mar, Hernández-Domínguez Xcaret Alexa, Arroyo-Helguera Omar
Format: Article
Language:English
Published: MDPI AG 2024-01-01
Series:Biology
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Online Access:https://www.mdpi.com/2079-7737/13/1/26
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author Reséndiz-Jiménez Arely
Arbez-Evangelista Cristian
Arroyo-Xochihua Omar
Palma-Jacinto José Antonio
Santiago-Roque Isela
De León-Ramírez Yeimy Mar
Hernández-Domínguez Xcaret Alexa
Arroyo-Helguera Omar
author_facet Reséndiz-Jiménez Arely
Arbez-Evangelista Cristian
Arroyo-Xochihua Omar
Palma-Jacinto José Antonio
Santiago-Roque Isela
De León-Ramírez Yeimy Mar
Hernández-Domínguez Xcaret Alexa
Arroyo-Helguera Omar
author_sort Reséndiz-Jiménez Arely
collection DOAJ
description 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.
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spelling doaj.art-f922f066887a49a989bddf488c27a43e2024-01-26T15:06:49ZengMDPI AGBiology2079-77372024-01-011312610.3390/biology13010026Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta CellsReséndiz-Jiménez Arely0Arbez-Evangelista Cristian1Arroyo-Xochihua Omar2Palma-Jacinto José Antonio3Santiago-Roque Isela4De León-Ramírez Yeimy Mar5Hernández-Domínguez Xcaret Alexa6Arroyo-Helguera Omar7Centro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa 91190, Veracruz, MexicoCentro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa 91190, Veracruz, MexicoCentro de Investigaciones Biomédicas, Universidad Veracruzana, Av. Luis Castelazo Ayala S/N, Col. Industrial Ánimas, Xalapa 91190, Veracruz, MexicoLaboratory of Biochemistry and Neurotoxicology, Faculty of Bioanalysis-Xalapa, Universidad Veracruzana, Médicos y Odontólogos S/N, Unidad del Bosque, Xalapa 91190, Veracruz, MexicoLaboratory of Biochemistry and Neurotoxicology, Faculty of Bioanalysis-Xalapa, Universidad Veracruzana, Médicos y Odontólogos S/N, Unidad del Bosque, Xalapa 91190, Veracruz, MexicoLaboratorio de Biomedicina y Salud Pública, Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Animas, Xalapa 91190, Veracruz, MexicoLaboratorio de Biomedicina y Salud Pública, Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Animas, Xalapa 91190, Veracruz, MexicoLaboratorio de Biomedicina y Salud Pública, Instituto de Salud Pública, Universidad Veracruzana, Av. Luís Castelazo Ayala S/N, Col. Industrial Animas, Xalapa 91190, Veracruz, MexicoBackground: 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.https://www.mdpi.com/2079-7737/13/1/26iodinepancreatic damageapoptosisGlut4
spellingShingle Reséndiz-Jiménez Arely
Arbez-Evangelista Cristian
Arroyo-Xochihua Omar
Palma-Jacinto José Antonio
Santiago-Roque Isela
De León-Ramírez Yeimy Mar
Hernández-Domínguez Xcaret Alexa
Arroyo-Helguera Omar
Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
Biology
iodine
pancreatic damage
apoptosis
Glut4
title Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
title_full Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
title_fullStr Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
title_full_unstemmed Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
title_short Iodine Promotes Glucose Uptake through Akt Phosphorylation and Glut-4 in Adipocytes, but Higher Doses Induce Cytotoxic Effects in Pancreatic Beta Cells
title_sort iodine promotes glucose uptake through akt phosphorylation and glut 4 in adipocytes but higher doses induce cytotoxic effects in pancreatic beta cells
topic iodine
pancreatic damage
apoptosis
Glut4
url https://www.mdpi.com/2079-7737/13/1/26
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