Anti-diabetes Effect of Zn(II)/Carnitine Complex by Oral Administration.

Yoshikawa, Yutaka; Ueda, Eriko; Kojima, Yoshitane

doi:10.1248/cpb.51.230

Cited by 38 publications

(23 citation statements)

References 17 publications

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“…One reported that oral administration of a zinc-carnitine complex lowered the high blood glucose levels and improved glucose tolerance in KK-A y mice with type 2 diabetes [14]. A more recent study [15] examined the effects of carnitine in liver-specific carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1)-deficient mice.…”

Section: Introductionmentioning

confidence: 99%

Carnitine revisited: potential use as adjunctive treatment in diabetes

et al. 2007

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Aims/hypothesis This study examined the efficacy of supplemental L-carnitine as an adjunctive diabetes therapy in mouse models of metabolic disease. We hypothesised that carnitine would facilitate fatty acid export from tissues in the form of acyl-carnitines, thereby alleviating lipidinduced insulin resistance. Materials and methods Obese mice with genetic or dietinduced forms of insulin resistance were fed rodent chow ± 0.5% L-carnitine for a period of 1-8 weeks. Metabolic outcomes included insulin tolerance tests, indirect calorimetry and mass spectrometry-based profiling of acyl-carnitine esters in tissues and plasma.Results Carnitine supplementation improved insulin-stimulated glucose disposal in genetically diabetic mice and wild-type mice fed a high-fat diet, without altering body weight or food intake. In severely diabetic mice, carnitine supplementation increased average daily respiratory exchange ratio from 0.886±0.01 to 0.914±0.01 (p<0.01), reflecting a marked increase in systemic carbohydrate oxidation. Similarly, under insulin-stimulated conditions, carbohydrate oxidation was higher and total energy expenditure increased from 172±10 to 210±9 kJ kg fatfree mass −1 h −1 in the carnitine-supplemented compared with control animals. These metabolic improvements corresponded with a 2.3-fold rise in circulating levels of acetyl-carnitine, which accounts for 86 and 88% of the total acyl-carnitine pool in plasma and skeletal muscle, respectively. Carnitine supplementation also increased several medium-and long-chain acyl-carnitine species in both plasma and tissues. Conclusions/interpretation These findings suggest that carnitine supplementation relieves lipid overload and glucose intolerance in obese rodents by enhancing mitochondrial efflux of excess acyl groups from insulin-responsive tissues. Carefully controlled clinical trials should be considered.

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Section: Introductionmentioning

confidence: 99%

Carnitine revisited: potential use as adjunctive treatment in diabetes

et al. 2007

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“…In genetically obese (ob/ob) mice, 20 mM ZnCl 2 in the drinking water for eight weeks reduced fasting plasma glucose levels by 21% and decreased fasting plasma insulin levels by 42%, as well as improving glucose tolerance, as tested by glucose load [29]. Very recently, a number of zinc complexes have been tested, both in vitro and in vivo, as ''insulinomimetics'' [30,31]. Among the complexes tested was bis(maltolato)zinc(II), Zn(ma) 2 [32], which normalized blood glucose levels in KKA y mice, a model of type 2 diabetes, when given i.p., 4.5 mg Zn kg À1 (69 lmol Zn) for 2 d followed by 2.0 mg Zn kg À1 (31 lmol Zn) for 12 d. In humans, supplementation with zinc, an essential trace element, had an unexpected negative impact on diabetic control [32].…”

Section: Introductionmentioning

confidence: 99%

Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes

Thompson

Chiles

Yuen

et al. 2004

Journal of Inorganic Biochemistry

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“…[34,35] These results demonstrate that following chronic oral gavage, [ZnA C H T U N G T R E N N U N G (tpps)] has a higher normoglycemic activity in KKA y mice than ZnSO 4 …”

Section: Resultsmentioning

confidence: 97%

A [meso‐Tetrakis(4‐sulfonatophenyl)porphyrinato]zinc(II) Complex As an Oral Therapeutic for the Treatment of Type 2 Diabetic KKA^y Mice

Saha

Yoshikawa

2007

ChemMedChem

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We prepared and characterized [meso-tetrakis(4-sulfonatophenyl)porphyrinato]zinc(II) ([Zn(tpps)]), and investigated its in vitro insulin-mimetic activity and in vivo hypoglycemic effect in type 2 diabetic KKA(y) mice. The results were compared with those of previously proposed insulin-mimetic zinc(II) complexes and zinc sulfate (ZnSO(4)). The in vitro insulin-mimetic activity of [Zn(tpps)] was considerably better than that of bis(allixinato)zinc(II) ([Zn(alx)(2)]), bis(maltolato)zinc(II) ([Zn(mal)(2)]), bis(2-aminomethylpyridinato)zinc(II) ([Zn(2-ampy)(2)](2+)), and ZnSO(4). In particular, the order of in vitro insulin-mimetic activity of the complexes was determined to be: [Zn(tpps)]>[Zn(alx)(2)]>[Zn(mal)(2)]>[Zn(2-ampy)](2+)>ZnSO(4). [Zn(tpps)] normalized the hyperglycemia of KKA(y) mice within 21 days when administered orally at doses of 10-20 mg (0.15-0.31 mmol) Zn per kg body mass for 28 days. In addition, metabolic syndromes such as insulin resistance, the degree of renal disturbance, and the degree of liver disturbance were significantly improved in [Zn(tpps)]-treated KKA(y) mice relative to those administered with saline and ZnSO(4). The improvement in diabetes was validated by the results of oral glucose-tolerance tests and the decrease in the HbA(1c) level observed. In contrast, ZnSO(4) and the ligand H(2)tpps did not lower the elevated blood glucose level under the same experimental conditions. Based on these observations, [Zn(tpps)] is proposed to be the first orally active zinc(II)-porphyrin complex for the efficacious treatment of not only type 2 diabetes but also metabolic syndromes in animals.

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Anti-diabetes Effect of Zn(II)/Carnitine Complex by Oral Administration.

Cited by 38 publications

References 17 publications

Carnitine revisited: potential use as adjunctive treatment in diabetes

Carnitine revisited: potential use as adjunctive treatment in diabetes

Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes

A [meso‐Tetrakis(4‐sulfonatophenyl)porphyrinato]zinc(II) Complex As an Oral Therapeutic for the Treatment of Type 2 Diabetic KKA^y Mice

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Anti-diabetes Effect of Zn(II)/Carnitine Complex by Oral Administration.

Cited by 38 publications

References 17 publications

Carnitine revisited: potential use as adjunctive treatment in diabetes

Carnitine revisited: potential use as adjunctive treatment in diabetes

Comparison of anti-hyperglycemic effect amongst vanadium, molybdenum and other metal maltol complexes

A [meso‐Tetrakis(4‐sulfonatophenyl)porphyrinato]zinc(II) Complex As an Oral Therapeutic for the Treatment of Type 2 Diabetic KKAy Mice

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A [meso‐Tetrakis(4‐sulfonatophenyl)porphyrinato]zinc(II) Complex As an Oral Therapeutic for the Treatment of Type 2 Diabetic KKA^y Mice