Evidence for the Improvement of Noninsulin-Dependent Diabetes Mellitus in KKAy Mice with Daily Oral Administration of Bis(6-methylpicolinato)oxovanadium(IV) Complex.

Fujisawa, Yae; Sakurai, Hiromu

doi:10.1248/cpb.47.1668

Cited by 32 publications

(17 citation statements)

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“…In addition to inorganic vanadium salts, several organo‐vanadium complexes, which include BMOV, bis(picolinato)oxo vanadium, bis (6‐methylpicolinato)oxovanadium), Vac, Vet and l ‐glutamic acid δ‐monohydroxamate‐NaOV complex [31,32,34–38], were also shown to exert an anti‐diabetic effect in animal models of Type I diabetes. These compounds also appeared to be more potent and had no significant gastrointestinal side‐effects [38,39].…”

Section: Effect On Animal Models Of Type 1 Diabetes Mellitusmentioning

confidence: 99%

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

2004

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Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes.

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Section: Effect On Animal Models Of Type 1 Diabetes Mellitusmentioning

confidence: 99%

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

2004

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“…114 In addition, [VO(6mpa) 2 ] was found to cause a hypoglycemic effect in a hereditary type 2 diabetic animal, the KK-A y mouse, as a result of daily ip injections and oral administrations. 115 In 2005, among 13 vanadyl analogue complexes of [VO(pa) 2 ] (Fig. 11), both bis(4-methylpicolinato)oxovanadium(IV) [VO(4mpa) 2 ] and bis(4-iodopicolinato)oxovanadium(IV) [VO(4ipa) 2 ] were found to be better at inhibiting FFA release and causing in vivo hypoglycemic effect in STZ-mice that received a single ip injection than the previously studied [VO(6mpa) 2 ] and [VO(5ipa) 2 ], 116 suggesting the importance of the substituent position on the ligand.…”

Section: Treatment Of Diabetes By Vanadium and Zinc Complexesmentioning

confidence: 99%

“…10). [VO(opt) 2 ] was actually the second example which could be used to treat both type 1 diabetic STZ-rats and type 2 obese diabetic ob/ob mice, 124 when administered via daily ip injections and orally, after [VO(6mpa) 2 ] in 1999. 115 The mechanism involving [VO(opt) 2 ] was examined. It is well known that TNF-is a key factor in the obesity-diabetes link, and elevate expression of TNF-is observed in the epidermal and subcutaneous fat tissue of ob/ob mice.…”

Section: Dinuclear Vanadyl Complexes Among Many Vanadyl Complexes Amentioning

confidence: 99%

Chemistry and Biochemistry of Insulin-Mimetic Vanadium and Zinc Complexes. Trial for Treatment of Diabetes Mellitus

Sakurai¹,

Katoh²,

Yoshikawa³

2006

Bulletin of the Chemical Society of Japan

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The number of patients suffering from diabetes mellitus (DM), which is a chronic metabolic disorder and mainly classified as either insulin-dependent type 1 or non-insulin-dependent type 2, is increasing throughout the world. The sequence of DM progression makes this disease a major health risk in regard to microvascular disease that leads to kidney failure, blindness, and nerve damage as well as macrovascular disease that leads to amputations, cardiovascular disease, and stroke. To treat DM, several types of insulin preparations and synthetic drugs for type 1 and type 2 DM, respectively, are in clinical use. However, there are several problems concerning the insulin preparations and synthetic drugs, such as physical and mental pain due to daily insulin injections and defects involving several side effects, respectively. Thus, the disease demands extraordinary effects to define pathobiochemical pathways and strategies for prevention and to find new therapeutic approaches. For this purpose, oxovanadium(IV) (vanadyl, VO 2þ ) and zinc(II) containing complexes have been explored as treatments for both types of DM. This article reviews the current state of research on insulin-mimetic and antidiabetic metal complexes, with special focus on paramagnetic vanadyl and diamagnetic zinc(II) complexes with different coordination modes, together with possible reaction mechanisms. New drug delivery systems involving enteric-coated capsulation and a biopolymer are also reviewed.One of the most important findings in the 20th century was that metal ions and their biomolecular complexes are essential for life on the earth and play roles in not only metalloproteins and metalloenzymes but also gene expression.1,2 This fundamental knowledge showed that our health, aging, physiological disorders and diseases are related to the state of the metal ions and their biomolecular complexes in our body. Some clinically useful metal-containing compounds and metal complexes known as metallopharmaceuticals that can regulate human health have been developed to treat or cure many types of diseases. The most distinctive examples are the platinum (Pt) anti-tumor agents, cisplatin and related newly developed Pt complexes, the gold (Au) orally active anti-rheumatoidal agent auronofin, the aluminum (Al) and zinc (Zn) anti-ulcer agents scralfate and polaprezinc, respectively, the selenium (Se) antiinflammatory agent ebselen, and the lithium (Li) anti-manicdepressive agent lithium carbonate.

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“…1), with particular emphasis on the efficacy of bis(picolinato) oxovanadium(IV) [VO(pa) 2 ] and bis(maltolato)oxovanadium(IV) [VO(mal) 2 ] complexes [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34]. These two complexes have advantages for examining the structure-activity relationship by adding suitable substituents on the picolinate [20][21][22][23][24][25][26][27][28][29][30] and 3-hydroxypyrone [31][32][33][34] as leading ligands, respectively. Among them, the complexes bis(6-methylpicolinato)oxovanadium(IV) [VO(6mpa) 2 ] and bis(allixinato)oxovanadium(IV) [VO(alx) 2 ] are expected to be especially applicable to clinical use.…”

Section: Introductionmentioning

confidence: 99%

New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes

Funakoshi

Adachi

2005

Pure and Applied Chemistry

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Abstract:The number of patients suffering from diabetes mellitus (DM) is increasing year by year throughout the world. In 2003, the world population was 6.3 billion, and the number of patients with DM in the adult population (20-79 years old) was 0.194 billion, which corresponded to 5.1 % of all disease incidence in that age range. In 2005, it is forecasted that the world population will increase to 8.0 billion and the ratio of DM to total disease incidence will increase to 6.3 %, with a disproportionate number of cases in Southeast Asia, the West Pacific, Central Asia, and North, Central, and South America. To treat Type 1 and Type 2 DM clinically, insulin preparations and synthetic drugs, respectively, have been used. However, these treatments are associated with some problems, such as several times of daily insulin injections following blood glucose monitoring and side effects in the case of the synthetic drugs. Consequently, a new class of therapeutic compounds is anticipated. After many trials, vanadium-containing complexes have been proposed to improve and treat both types of DM by in vivo experiments. We present an overview of insulinomimetic and antidiabetic vanadyl (+4 vanadium, V) complexes, and propose new candidates for dinuclear vanadyl complexes with naturally occurring ligands. The current state of research on the dinuclear vanadyl(IV)-tartrate complexes is described in regard to the physicochemical characteristics, in vitro insulinomimetic and in vivo blood-glucose-lowering effects of the prepared complexes.

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Evidence for the Improvement of Noninsulin-Dependent Diabetes Mellitus in KKAy Mice with Daily Oral Administration of Bis(6-methylpicolinato)oxovanadium(IV) Complex.

Cited by 32 publications

References 1 publication

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

Insulino‐mimetic and anti‐diabetic effects of vanadium compounds

Chemistry and Biochemistry of Insulin-Mimetic Vanadium and Zinc Complexes. Trial for Treatment of Diabetes Mellitus

New developments of insulinomimetic dinuclear vanadyl(IV)-tartrate complexes

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