Anti-diabetic effect of a preparation of vitamins, minerals and trace elements in diabetic rats: a gender difference

Sárközy, Márta; Fekete, Veronika; Szűcs, Gergő; Török, Szilvia; Szűcs, Csilla; Bárkányi, Judit; Varga, Zoltán V.; Földesi, Imre; Csonka, Csaba; Kónya, Csaba; Csont, Tamás; Ferdinándy, Péter

doi:10.1186/1472-6823-14-72

Cited by 15 publications

(20 citation statements)

References 46 publications

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“…CLE contains diverse types of chemical constituents, such as polyphenols [ 9 ], minerals, dietary fiber, vitamin A, vitamin C, and several essential unsaturated fatty acids [ 10 ]. Their anti-diabetic activities have already been reported [ 28 , 29 ]. The synergistic actions of such components could effectively regulate blood glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes

2015

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BackgroundGlucose homeostasis is distorted by defects of the PI3K/AKT and AMPK pathways in insulin-sensitive tissues, allowing the accumulation of glucose in the blood. The purpose of this study was to assess the effects and mechanisms by which ethanol extract of Caulerpa lentillifera (CLE) regulates glucose metabolism in C57BL/KsJ-db/db (db/db) mice.MethodsMice were administered CLE (250 or 500 mg/kg BW) or rosiglitazone (RSG, 10 mg/kg BW) for 6 weeks. Then, oral glucose tolerance test (OGTT) and intraperitoneal insulin tolerance test (IPITT) were performed, and blood glucose was measured in db/db mice. Levels of insulin and insulin resistance factors in plasma, glycogen content in the liver, and IRS, PI3K, AKT, and GLUT4 expressions in skeletal muscles were measured in db/db mice. Glucose uptake and insulin signaling molecules were measured in L6 myocytes, using fluorometry and Western blotting.ResultsCLE significantly decreased fasting blood glucose, glucose level in OGTT and IPITT, plasma insulin, homeostatic model assessment-insulin resistant (HOMA-IR), TNF-α, IL-6, FFA, TG and TC levels, and hepatic glycogen content in db/db mice. CLE significantly increased the activation of IRS, AKT, PI3K, and GLUT4, which are the key effector molecules of the PI3K/AKT pathway in L6 myocytes and the skeletal muscles of db/db mice. The enhanced glucose uptake by CLE was abolished by treatment with a PI3K inhibitor (LY294002), but not by an AMPK inhibitor (compound C) in L6 myocytes. CLE regulated glucose uptake and homeostasis via the PI3K/AKT pathway in myocytes and db/db mice, respectively.ConclusionOur results suggest that CLE could be a potential candidate for the prevention of diabetes.

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Section: Discussionmentioning

confidence: 99%

Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes

2015

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“…Blood samples were collected from the saphenous vein after overnight fasting. Blood glucose level was immediately determined by a standard glucose meter in duplicates (Accutrend GCT, Roche Diagnostics, Mannheim, Germany) as described previously [ 33 – 36 ].…”

Section: Methodsmentioning

confidence: 99%

“…To monitor the effect of cholesterol and cholic acid enriched diet on the endocrine pancreas, plasma insulin levels were measured by an enzyme immunoassay (Mercodia, Ultrasensitive Rat Insulin ELISA) in duplicates according to the manufacturer’s instructions as described previously [ 33 – 36 ].…”

Section: Methodsmentioning

confidence: 99%

Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

et al. 2017

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BackgroundLipid accumulation in the liver and pancreas is primarily caused by combined hyperlipidemia. However, the effect of isolated hypercholesterolemia without hypertriglyceridemia is not fully described. Therefore, our aim was to investigate whether hypercholesterolemia alone leads to alterations both in hepatic and pancreatic lipid panel and histology in rats.MethodsMale Wistar rats were fed with 2% cholesterol +0.25% cholate-supplemented diet or standard chow for 12 weeks. Blood was collected at weeks 0, 4, 8 and 12 to measure serum cholesterol and triglyceride levels. At week 12, both the pancreas and the liver were isolated for further histological and biochemical analysis. Hepatic and plasma fatty acid composition was assessed by gas chromatography. Expression of mRNA of major enzymes involved in saturated/unsaturated fatty acid synthesis was analyzed by qPCR. In separate experiments serum enzyme activities and insulin levels were measured at week 9.ResultsAt week 12, rats fed with 2% cholesterol +0.25% cholate-supplemented diet were characterized by elevated serum cholesterol (4.09 ± 0.20 vs. 2.89 ± 0.22 mmol/L, *p < 0.05) while triglyceride (2.27 ± 0.05 vs. 2.03 ± 0.03 mmol/L) and glucose levels (5.32 ± 0.14 vs. 5.23 ± 0.10 mmol/L) remained unchanged. Isolated hypercholesterolemia increased hepatic lipid accumulation, hepatic cholesterol (5.86 ± 0.22 vs. 1.60 ± 0.15 ng/g tissue, *p < 0.05) and triglyceride contents (19.28 ± 1.42 vs. 6.78 ± 0.71 ng/g tissue, *p < 0.05), and hepatic nitrotyrosine level (4.07 ± 0.52 vs. 2.59 ± 0.31 ng/mg protein, *p < 0.05). The histology and tissue lipid content of the pancreas was not affected. Serum total protein level, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities remained unchanged in response to isolated hypercholesterolemia while serum alkaline phosphatase activity (ALP) significantly increased. Plasma insulin levels did not change in response to isolated hypercholesterolemia suggesting an intact endocrine function of the pancreas. Isolated hypercholesterolemia caused a significantly increased hepatic and serum fatty acid level associated with a marked alteration of fatty acid composition. Hepatic expression of Δ9-desaturase (SCD1) was increased 4.92×, while expression of Δ5-desaturase and Δ6-desaturase were decreased (0.447× and 0.577×, respectively) due to isolated hypercholesterolemia.ConclusionsIsolated hypercholesterolemia leads to hepatic steatosis and marked alterations in the hepatic lipid profile without affecting the pancreas. Altered fatty acid profile might mediate harmful effects of cholesterol in the liver.

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“…The injection of neonatal rats with streptozotocin (STZ) is a well characterized and recognized model of diabetes mellitus [ 24 – 27 ]. This model has been particularly characterized in detail in our previous study [ 14 ]. STZ is toxic especially to pancreatic β-cells.…”

Section: Methodsmentioning

confidence: 99%

“…However, the literature is limited and controversial on the potential beneficial effects of these complex preparations containing more than 3 components on disease progression [ 12 – 16 ]. We have recently shown that chronic treatment with a MVT preparation improved well-established diagnostic markers of DM such as fasting blood glucose, HbA1c, glucose tolerance, and serum insulin levels in male diabetic rats [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats

Sárközy

Szűcs

Pipicz

et al. 2015

Cardiovasc Diabetol

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BackgroundDiabetic patients have an increased risk of developing cardiovascular diseases, which are the leading cause of death in developed countries. Although multivitamin products are widely used as dietary supplements, the effects of these products have not been investigated in the diabetic heart yet. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) affects the cardiac gene expression pattern in experimental diabetes.MethodsTwo-day old male Wistar rats were injected with streptozotocin (i.p. 100 mg/kg) or citrate buffer to induce diabetes. From weeks 4 to 12, rats were fed with a vehicle or a MVT preparation. Fasting blood glucose measurement and oral glucose tolerance test were performed at week 12, and then total RNA was isolated from the myocardium and assayed by rat oligonucleotide microarray for 41012 oligonucleotides.ResultsSignificantly elevated fasting blood glucose concentration and impaired glucose tolerance were markedly improved by MVT-treatment in diabetic rats at week 12. Genes with significantly altered expression due to diabetes include functional clusters related to cardiac hypertrophy (e.g. caspase recruitment domain family, member 9; cytochrome P450, family 26, subfamily B, polypeptide; FXYD domain containing ion transport regulator 3), stress response (e.g. metallothionein 1a; metallothionein 2a; interleukin-6 receptor; heme oxygenase (decycling) 1; and glutathione S-transferase, theta 3), and hormones associated with insulin resistance (e.g. resistin; FK506 binding protein 5; galanin/GMAP prepropeptide). Moreover the expression of some other genes with no definite cardiac function was also changed such as e.g. similar to apolipoprotein L2; brain expressed X-linked 1; prostaglandin b2 synthase (brain). MVT-treatment in diabetic rats showed opposite gene expression changes in the cases of 19 genes associated with diabetic cardiomyopathy. In healthy hearts, MVT-treatment resulted in cardiac gene expression changes mostly related to immune response (e.g. complement factor B; complement component 4a; interferon regulatory factor 7; hepcidin).ConclusionsMVT-treatment improved diagnostic markers of diabetes. This is the first demonstration that MVT-treatment significantly alters cardiac gene expression profile in both control and diabetic rats. Our results and further studies exploring the mechanistic role of individual genes may contribute to the prevention or diagnosis of cardiac complications in diabetes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-015-0248-6) contains supplementary material, which is available to authorized users.

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Anti-diabetic effect of a preparation of vitamins, minerals and trace elements in diabetic rats: a gender difference

Cited by 15 publications

References 46 publications

Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes

Caulerpa lentillifera extract ameliorates insulin resistance and regulates glucose metabolism in C57BL/KsJ-db/db mice via PI3K/AKT signaling pathway in myocytes

Isolated hypercholesterolemia leads to steatosis in the liver without affecting the pancreas

The effect of a preparation of minerals, vitamins and trace elements on the cardiac gene expression pattern in male diabetic rats

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