Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells
The reaction of the vanadyl ion (VO<sup>2+</sup>) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and p...
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2024-02-01
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author | Vital Ugirinema Frank Odei-Addo Carminita L. Frost Zenixole R. Tshentu |
author_facet | Vital Ugirinema Frank Odei-Addo Carminita L. Frost Zenixole R. Tshentu |
author_sort | Vital Ugirinema |
collection | DOAJ |
description | The reaction of the vanadyl ion (VO<sup>2+</sup>) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid–base titrations. The species distribution diagrams for the high-molecular-mass (HMM) proteins with oxidovanadium(IV) under physiological pH were dominated by VO(HMM)<sub>2</sub>, VOL(HMM) for unsubstituted ligands (L<sup>−</sup> = Im4COO<sup>−</sup> and Im2COO<sup>−</sup>). However, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH were dominated by VOL<sub>2</sub>, VO(HMM)<sub>2</sub> and VO<sub>2</sub>L<sub>2</sub>(HMM). These species were further confirmed by LC-MS, MALDI-TOF-MS and EPR studies. The glucose-stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at a 1 µM concentration, which was established through cytotoxicity studies via the MTT assay. The neutral complexes, especially VO(MeIm2COO)<sub>2</sub>, showed promising results in the stimulation of insulin secretion than the cationic [VO(MeIm2CH<sub>2</sub>OH)<sub>2</sub>]<sup>2+</sup> complex and the vanadium salt. Oxidovanadium(IV) complexes reduced insulin stimulation significantly under normoglycaemic levels but showed positive effects on insulin secretion under hyperglycaemic conditions (33.3 mM glucose media). The islets exposed to oxidovanadium(IV) complexes under hyperglycaemic conditions displayed a significant increase in the stimulatory index with 1.19, 1.75, 1.53, 1.85, 2.20 and 1.29 observed for the positive control (sulfonylurea:gliclazide), VOSO<sub>4</sub>, VO(Im4COO)<sub>2</sub>, VO(Im2COO)<sub>2</sub>, VO(MeIm2COO)<sub>2</sub> and VO(MeIm2CH<sub>2</sub>OH)<sub>2</sub><sup>2+</sup>, respectively. This observation showed a potential further effect of vanadium complexes towards type 2 diabetes and has been demonstrated for the first time in this study. |
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spelling | doaj.art-e47ab184b2f742e3884ef17df3cb53922024-02-09T15:19:12ZengMDPI AGMolecules1420-30492024-02-0129372410.3390/molecules29030724Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic CellsVital Ugirinema0Frank Odei-Addo1Carminita L. Frost2Zenixole R. Tshentu3Department of Chemistry, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South AfricaDepartment of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South AfricaDepartment of Biochemistry and Microbiology, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South AfricaDepartment of Chemistry, Nelson Mandela University, P.O. Box 77000, Port Elizabeth 6031, South AfricaThe reaction of the vanadyl ion (VO<sup>2+</sup>) with imidazole-4-carboxylic acid (Im4COOH), imidazole-2-carboxylic acid (Im2COOH) and methylimidazole-2-carboxylic acid (MeIm2COOH), respectively, in the presence of small bioligands (bL) [oxalate (Ox), lactate (Lact), citrate (Cit) and phosphate (Phos)] and high-molecular-weight (HMW) human serum proteins [albumin (HSA) and transferrin (hTf)] were studied in aqueous solution using potentiometric acid–base titrations. The species distribution diagrams for the high-molecular-mass (HMM) proteins with oxidovanadium(IV) under physiological pH were dominated by VO(HMM)<sub>2</sub>, VOL(HMM) for unsubstituted ligands (L<sup>−</sup> = Im4COO<sup>−</sup> and Im2COO<sup>−</sup>). However, for the N-substituted MeIm2COOH, the species distribution diagrams under physiological pH were dominated by VOL<sub>2</sub>, VO(HMM)<sub>2</sub> and VO<sub>2</sub>L<sub>2</sub>(HMM). These species were further confirmed by LC-MS, MALDI-TOF-MS and EPR studies. The glucose-stimulated insulin secretion (GSIS) action of the complexes was investigated using INS-1E cells at a 1 µM concentration, which was established through cytotoxicity studies via the MTT assay. The neutral complexes, especially VO(MeIm2COO)<sub>2</sub>, showed promising results in the stimulation of insulin secretion than the cationic [VO(MeIm2CH<sub>2</sub>OH)<sub>2</sub>]<sup>2+</sup> complex and the vanadium salt. Oxidovanadium(IV) complexes reduced insulin stimulation significantly under normoglycaemic levels but showed positive effects on insulin secretion under hyperglycaemic conditions (33.3 mM glucose media). The islets exposed to oxidovanadium(IV) complexes under hyperglycaemic conditions displayed a significant increase in the stimulatory index with 1.19, 1.75, 1.53, 1.85, 2.20 and 1.29 observed for the positive control (sulfonylurea:gliclazide), VOSO<sub>4</sub>, VO(Im4COO)<sub>2</sub>, VO(Im2COO)<sub>2</sub>, VO(MeIm2COO)<sub>2</sub> and VO(MeIm2CH<sub>2</sub>OH)<sub>2</sub><sup>2+</sup>, respectively. This observation showed a potential further effect of vanadium complexes towards type 2 diabetes and has been demonstrated for the first time in this study.https://www.mdpi.com/1420-3049/29/3/724vanadiumbiospeciationdiabetesglucose-stimulated insulin secretion |
spellingShingle | Vital Ugirinema Frank Odei-Addo Carminita L. Frost Zenixole R. Tshentu Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells Molecules vanadium biospeciation diabetes glucose-stimulated insulin secretion |
title | Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells |
title_full | Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells |
title_fullStr | Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells |
title_full_unstemmed | Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells |
title_short | Biospeciation of Oxidovanadium(IV) Imidazolyl–Carboxylate Complexes and Their Action on Glucose-Stimulated Insulin Secretion in Pancreatic Cells |
title_sort | biospeciation of oxidovanadium iv imidazolyl carboxylate complexes and their action on glucose stimulated insulin secretion in pancreatic cells |
topic | vanadium biospeciation diabetes glucose-stimulated insulin secretion |
url | https://www.mdpi.com/1420-3049/29/3/724 |
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