A perspective on the role of metals in diabetes: past findings and possible future directions

Meyer, Jennifer A.; Spence, Dana M.

doi:10.1039/b817203j

Cited by 68 publications

(54 citation statements)

References 155 publications

(153 reference statements)

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“…Patients with diabetes suffer from hypozincemia as a result of failure of ␤-cell production, which finally affects insulin levels [19]. Our results are consistent with this finding as we detected a 1.8-fold higher Zn concentration in healthy rats than in diabetic ones after sodium tungstate treatment (Table 2).…”

Section: W Accumulation In Diabetic and Healthy Rats After Treatment supporting

confidence: 91%

“…It has been reported that levels of GSH, an abundant antioxidant metabolite present in cells at mM level, are lower in patients suffering from diabetes [21]. Metals like Cu, Mn, Mg, Fe, Se, V, Cr and Zn have been proposed to indirectly participate in the reversal of oxidative stress [19], with some establishing complexes with GSH, as shown for V [22].…”

Section: Interaction Of W With Glutathionementioning

confidence: 99%

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Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate

Gómez-Gómez

Fariñas

Cañas-Montalvo

et al. 2011

Talanta

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a b s t r a c tIt is known that oral administration of sodium tungstate preserves the pancreatic beta cell function in diabetic rats. Healthy and streptozotocin-induced diabetic rats were treated with sodium tungstate for one, three or six weeks, after which the species of W in serum, were analysed. An increase in serum W with treatment time was observed. After six weeks, the serum W concentration in diabetic rats (70 mg L −1 ) was about 4.6 times higher than in healthy specimens. This different behaviour was also observed for Cu accumulation, while the Zn pattern follows the contrary. The patterns observed in the retention of Cu and Zn may be attributable to a normalization of glycaemia. The speciation analysis of W was performed using 2D separations, including an immunoaffinity packing and a SEC (Size Exclusion Chromatography) column coupled to an ICP-MS (Inductively Coupled Plasma Mass Spectrometry) for elemental detection. Ultrafiltration data together with SEC-ICP-MS results proved that around 80% of serum W was bound to proteins, the diabetic rats registering a higher W content than their healthy counterparts. Most of the proteinbound W was due to a complex with albumin. An unknown protein with a molecular weight higher than 100 kDa was also found to bind a small amount of W (about 2%). MALDI-TOF (Matrix-Assisted Laser Desorption Ionization Time-of-Flight) analysis of the desalted and concentrated chromatographic fractions confirmed albumin as the main protein bound to tungstate in rat serum, while no binding to transferrin (Tf) was detected. The interaction between glutathione and W was also evaluated using standard solutions; however, the formation of complexes was not observed. The stability of the complexes between W and proteins when subjected to more stringent procedures, like those used in proteomic methodologies (denaturing with urea or SDS, boiling, sonication, acid media, reduction with ␤-mercaptoethanol (BME) or DTT (dithiotreitol) and alkylation with iodoacetamide (IAA), was also evaluated. Our results indicate that the stability of the complexes between W and proteins is not too high enough to remain unaltered during protein separation by SDS-PAGE in denaturing and reducing conditions. However, the procedures for in-solution tryptic digestion and for ESI-MS analysis in MeOH/H 2 O/with 0.1% formic acid could be used for protein identification without large loss of binding between W and proteins.Crown

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Section: W Accumulation In Diabetic and Healthy Rats After Treatment supporting

confidence: 91%

Section: Interaction Of W With Glutathionementioning

confidence: 99%

Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate

Gómez-Gómez

Fariñas

Cañas-Montalvo

et al. 2011

Talanta

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“…Quarterman et al [45] reported that diet induced zinc deficiency in rats resulted in a decrease in the ability of the pancreas to secrete insulin in response to a glucose load. Meyer and Spence [46] indicated that decreased zinc in the pancreas may reduce the ability of the islet b-cells to produce and secrete insulin and zinc deficiency is positively correlated with diabetes and may also affect the progress of Type 2 diabetes [47].…”

Section: F CLmentioning

confidence: 99%

Synthesis and Characterization of Nano-doped Zinc Oxide and its Application as Protective Oxidative Changes in the Retina of Diabetic Rats

El-Rahman¹,

Sm²,

Al-Ghannam³

2016

J Diabetes Metab

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Oxidative stress is a basic mechanism behind the development of diabetic retinopathy (DR). Therefore, the present study conducted to evaluate the protective effect of zinc oxide nanoparticles (ZnONPs) doped with fluorine (F:ZnO) and chlorine (Cl:ZnO), on retinal oxidative stress in type II diabetic rats. TEM showed that the F:ZnO and Cl:ZnO have average particle size 17.7 and 59.3 nm, respectively. The results indicated that serum glucose was increased significantly (p ≤ 0.05) and serum insulin was decreased significantly 3 days after treatment with STZ compared to other groups. STZ treatment depleted both retinal and liver TBA and retinal GST contents. While, simultaneous treatment rats with low and high dose of STZ + F:ZnO and STZ + Cl:ZnO were decreased serum glucose induced by STZ and reversed the deplete influence on GSH level of retinal and reduced the highs in TBA levels of livers and retinas in STZ -administrated rats. The results investigate the useful effects of high dose of F:ZnO and Cl:ZnO in protection diabetic rats against hyperglycemia and retina against oxidative stress.

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“…Following collection of plasma samples, organs (liver, muscle, adipose, pancreas, femur, and kidney) were dissected, weighed and heated repeatedly at approximately 200°C with 60% HNO 3 , 60% HClO 4 , and 30% H 2 O 2 in 50 ml tall beakers. When the residues became white powder, the samples were dissolved in 1% HNO 3 . The Zn concentrations were determined by a graphite furnace atomic absorption spectrometer (AAS; AA-630 and GFA-EX7i, Shimadzu Co., Kyoto, Japan).…”

Section: Administration Of Zinc Complexes In Kk-a Y Micementioning

confidence: 99%

“…2) For many years, the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized and discussed. 3) We have developed anti-diabetic metal complexes as new candidates for hypoglycemic agents. Since 2000, we have proposed several types of zinc(II) (Zn) complexes with various coordination modes, [4][5][6][7][8] in which Zn complexes with Zn(O 4 ) and Zn(N 2 O 2 ) coordination environments showed anti-diabetic effect on oral administration.…”

mentioning

confidence: 99%

Oral Administration of Bis(aspirinato)zinc(II) Complex Ameliorates Hyperglycemia and Metabolic Syndrome-Like Disorders in Spontaneously Diabetic KK-Ay Mice: Structure-Activity Relationship on Zinc-Salicylate Complexes

Yoshikawa

Adachi

Yasui

et al. 2011

CHEMICAL & PHARMACEUTICAL BULLETIN

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The number of patients suffering from diabetes mellitus in the 21st century is increasing worldwide.1) Several types of injectable insulin preparations are available for patients with type 1 diabetes, characterized by progressive b-cell destruction and deficiency of intrinsic insulin secretion. On the other hand, various types of synthetic pharmaceutics are clinically used for the treatment of type 2 diabetes, characterized by insulin resistance. In recent years, new types of anti-diabetic pharmaceutics such as glucagon-like peptide-1 (GLP-1) receptor agonist and dipeptidyl peptidase-4 (DPP-4) inhibitors are developed and clinically available for treatment. 2)For many years, the relationship between diabetes and biometals such as vanadium, copper, and zinc ions has been recognized and discussed.3) We have developed anti-diabetic metal complexes as new candidates for hypoglycemic agents. Since 2000, we have proposed several types of zinc(II) (Zn) complexes with various coordination modes, [4][5][6][7][8] in which Zn complexes with Zn(O 4 ) and Zn(N 2 O 2 ) coordination environments showed anti-diabetic effect on oral administration. 9)Coincidently, a high dose of salicylates was found to reverse hyperglycemia and hyperinsulinemia in type 2 diabetic patients.10) These findings strongly suggest that the combined use of Zn and salicylates achieves the synergism in treating diabetes. We then tried to use aspirin (acetylsalicylic acid) and its related compounds with two oxygen atoms as ligand to Zn.Salicylic acid, a colorless crystalline organic acid, functions as a plant hormone.11) It is probably the best known compound that is chemically similar but not identical to the active component of aspirin. The medicinal property of salicylic acid has been known mainly for pain and fever relieves since ancient times. A side effect of salicylic acid such as stomachache, however, was replaced by aspirin with low side effect. Aspirin, which is a medicine in the family of salicylates, has been used as an analgesic, anti-pyretic, and antiinflammatory. 12,13) It has also an anti-platelet effect with low doses to prevent both heart attacks and thrombus formation in hyper-coagulate states.14,15) On the other hand, over 100 years ago, a high-dose salicylic acid treatment was reported to reduce the glycosuria in type 2 diabetic patients.16) Later in 1957, treatment of diabetes with aspirin for 10-14 d was found to improve the impaired oral glucose tolerance test in the diabetic patients.17) The mechanism how salicylic acid may affect the whole-body glucose homeostasis remains unknown until a recent finding that salicylic acid inhibits the activity of inhibitory kB kinase-b (IKKb), a known serine kinase. 10,18,19) In light of these findings, we hypothesized that Zn-salicylate complexes might be effective for not only treating type 2 diabetes and its complications but also improving metabolic syndrome. To verify this hypothesis, we have examined whether Zn-salicylate complexes containing Zn-aspirin complex show the anti-diabetic activi...

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A perspective on the role of metals in diabetes: past findings and possible future directions

Cited by 68 publications

References 155 publications

Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate

Biospeciation of tungsten in the serum of diabetic and healthy rats treated with the antidiabetic agent sodium tungstate

Synthesis and Characterization of Nano-doped Zinc Oxide and its Application as Protective Oxidative Changes in the Retina of Diabetic Rats

Oral Administration of Bis(aspirinato)zinc(II) Complex Ameliorates Hyperglycemia and Metabolic Syndrome-Like Disorders in Spontaneously Diabetic KK-Ay Mice: Structure-Activity Relationship on Zinc-Salicylate Complexes

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