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

Abstract

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.

Transcriptomic alterations in the heart of non-obese type 2 diabetic Goto-Kakizaki rats

“…As described previously, rats were fasted overnight (12 h) prior to serum glucose level measurements and OGTTs (weeks 7, 11 and 15) to verify the development of hyperglycemia and glucose-intolerance as diagnostic criteria of diabetes mellitus [ 21 , 22 , 36 ]. Blood samples were collected from the saphenous vein.…”

“…We have previously shown that cardiac gene expression pattern is significantly altered in obese ZDF rats, a model of T2DM and metabolic syndrome [ 21 ], and in streptozotocin-induced T1DM rats [ 22 ] at the transcript level. The effect of non-obese T2DM on gene expression pattern in various tissue types has been investigated in a few studies.…”

Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway

“…The accumulation of extracellular matrix proteins, in particular collagens is one of the key processes in DCM. Sárközy et al have shown an altered expression of several genes related to cardiac hypertrophy and remodeling [ 41 ]. Minerals, vitamins, and trace elements treatment in diabetic rats resulted in opposite gene expression changes, showing beneficial effects in DCM [ 41 ].…”

“…Sárközy et al have shown an altered expression of several genes related to cardiac hypertrophy and remodeling [ 41 ]. Minerals, vitamins, and trace elements treatment in diabetic rats resulted in opposite gene expression changes, showing beneficial effects in DCM [ 41 ]. In the present study enhanced nitro-oxidative stress and apoptosis in the diabetic myocardium, and a high histopathological cardiac fibrosis score were shown in accordance with the literature, and were proven to be normalized by a Zn(ASA) 2 treatment.…”

Selenoprotein S: a therapeutic target for diabetes and macroangiopathy?

“…Selenium (Se), a trace element, is a key component of selenoproteins involved in a wide range of functions, including redox homeostasis, inflammatory regulation, thyroid hormone metabolism, immunity, myocardial and tumoral diseases, and reproduction [ 3 – 6 ]. Moreover, it is well documented that Se is associated with glucose metabolism, and both over supplementation and deficiency of Se can be associated with type 2 DM (T2DM) risk, following a U-shaped curve [ 3 , 7 , 8 ]. Selenoproteins are important metabolites of dietary Se, fulfilling the catalytic effects of Se, and are characterized by a selenocysteine (Sec), a selenium-containing amino acid encoded from the stop codon UGA in the molecular structure [ 9 – 12 ].…”