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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Main Authors: Vital Ugirinema, Frank Odei-Addo, Carminita L. Frost, Zenixole R. Tshentu
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/29/3/724
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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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