EURO-ECO 2010Hanover2 - 3 Dezember 2010 |
Environmental, Engineering - Economic and Legal Aspects for Sustainable Living |
European Academy of Natural Sciences, HanoverEuropean Scientific Society, HanoverUniversity of Bremen, Bremen |
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| M.M. Korneeva V.Yu. Bashmakov V.N. Popov |
FREE FATTY ACIDS AS A POTENTIAL PHARMACOLOGICAL AGENT FOR THE CORRECTION OF DIABETES - RELATED PATHOLOGIES |
| Voronezh State University, Voronezh, Russia |
Diabetes mellitus being one of the most significant concerns is the top priority of many healthcare systems. The world prevalence of diabetes among adults (aged 20–79 years) is 6.4%, affecting 285 million adults, in 2010, and will increase to 7.7%, and 439 million adults by 2030. Between 2010 and 2030, there will be a 69% increase in numbers of adults with diabetes in developing countries and a 20% increase in developed countries. These predictions, based on a larger number of studies than previous estimates, indicate a growing burden of diabetes, particularly in developing countries.
There are 2 types of Diabetes. Type 1 called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes. It develops when the body’s immune system destroys pancreatic beta cells. This cells produce hormone insulin that regulates blood glucose. This form of diabetes usually strikes children and young adults, although disease onset can occur at any age. Risk factors for type 1 diabetes may be autoimmune, genetic, or environmental. Type 2 diabetes called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. It usually begins as insulin resistance, a disorder in which the cells do not use insulin properly. As the need for insulin rises, the pancreas gradually loses its ability to produce it. This type of diabetes is associated with older age, obesity, family history of diabetes, history of gestational diabetes, impaired glucose metabolism, physical inactivity, and race/ethnicity. Other types of diabetes result from specific genetic conditions, such as maturity-onset diabetes of youth; surgery; medications; infections; pancreatic disease; and other illnesses. Such types of diabetes account for 1 to 5 percent of all diagnosed cases. The UCPs protein family could be stimulated by fatty acids resulting in reduction of ROS generation. It was shown that UCP2 expression increased dramatically undo diabetes.
In our experiments we used alloxane as a chemical inductor of diabetes. 150 mg per kg of rat weight were injected intraperitoneal (intraperitoneal, intra-abdominal). Glucose level was controlled by glucose oxidase system and increased at least twice after injection. Previously it was shown that free fatty acids act as the uncoupling and protector against reactive oxygen species production and that adequate antioxidant therapy can prevent oxidative stress – key etiological factor for many diseases including diabetes. We have studied the expression of genes encoding UCP2 and ANT under the condition of experimental type I diabetes and antioxidant therapy. The experiments were conducted on pedigreeless male rats (Rattus norvegicus L.). Alloxan-treated rats were divided into two groups. Some animals have received 250 nM targeted antioxidant SkQ1 solution with water. Others were given water without SkQ1. Total RNA was obtained by phenol-chloroform extraction method with LiCl. Reverse transcription was performed according to manufacturer’s protocol («Fermentas»). cDNA was amplified by qPCR with SYBR Green I. The program was: 94 °C 20 seconds; 56 °Ñ 35 seconds; 71 °C 45 seconds. It was shown that in pancreas UCP2 mRNA expression under the condition of mitochondrial-addressed antioxidant therapy is 2,2-fold less than in alloxan-treated rats without the therapy. That means that the process of uncoupling as well as UCPs becomes unnecessary when transmembrane potential growth is suppressed by the antioxidant action. The similar situation was observed with ant gene, but the difference was more considerable. The expression level under SkQ1 treatment was 5-fold less than under the conditions of alloxan diabetes.
The fibrates are a class of amphipathic carboxylic acids have been used for the treatment of hypertriglyceridemia or mixed hyperlipidemia for >30 years. It is now known that fibrates act by stimulating the activity of peroxisome proliferator-activated receptor (PPAR). Now we have started experiments with fibrates treatment to check the hypothesis that activation of lipid degradation through PPAR could results in “mild” uncoupling, ROS production reduction and potential preservation of pancreas undo alloxane treatment.
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