Brain spingolipids in hyperglycemia

• Autorzy: Car H. , Fiedorowicz A. , Prokopiuk S. , Bienias K. , Zendzian-Piotrowska M. , Chabowski A. , Kosacka I. , Tidhar R. , Futerman A.H. , Glombik K. , Basta-Kaim A.
• Języki publikacji: EN

Abstrakty

EN

Ceramide (Cer) and sphingomyelin (SM) are members of sphingolipid (SL) family. Their concentrationsin the brain undergo substantial changes in many pathologies. They are also important players in diabetes-linked brain dysfunctions, in which increased content of ceramides can be toxic to neurons. The aim of the study was to evaluate selected parameters of sphingolipids and insulin pathways in prefrontal cortex (PC) and hippocampus (H) of rats with experimentally induced hyperglycemia. STZ-rat model of type 1 diabetes and high fat diet model of insulin resistance were used. Analyses of studied parameters were performed by GLC, IHC and Elisa. We found the augmented levels of ceramides in H and PC and only minor in striatum and cerebellum of rats with STZ-induced diabetes. Similar expressions of Cer were confirmed by IHC. Myriocin, an inhibitor of an enzyme of ceramide de novo synthesis pathway, reduced ceramide generation in hyperglycemic brains, particularly in PC, which was reflected in altered Cer synthase activities. In addition, we reported the fluctuations in sphingomyelin levels in investigated structures. The level of insulin did not change in H and PC of STZ-treated rats. An expression of insulin receptor and its phosphorylated form decreased in both structures, but was restored after myriocin administration. Similarly, Akt and phosphorylated Akt changed in these structures suggesting important role of de novo Cer synthesis in intracellular pathways of insulin. In the rat model of high fat diet, which leads to insulin resistance, the sphingolipid pattern (Cer and SM) was altered in H and PC as well. Metformin, the drug of choice in diabetes type 2, influenced the content of the above SLs in these structures, suggesting the additional central activity of antidiabetic treatment. We conclude that ceramide and SM may be important mediators of diabetes- accompanied brain dysfunction.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S15

Twórcy

autor

Car H.

• Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland

autor

Fiedorowicz A.

• Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Bialystok, Poland

autor

Prokopiuk S.

• Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland

autor

Bienias K.

• Department of Experimental Pharmacology, Medical University of Bialystok, Bialystok, Poland

autor

Zendzian-Piotrowska M.

• Department of Physiology, Medical University of Bialystok, Bialystok, Poland

autor

Chabowski A.

• Department of Physiology, Medical University of Bialystok, Bialystok, Poland

autor

Kosacka I.

• Department of Histology and Cytophysiology, Medical University of Bialystok, Bialystok, Poland

autor

Tidhar R.

• Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

autor

Futerman A.H.

• Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel

autor

Glombik K.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, Krakow, Poland

autor

Basta-Kaim A.

• Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, Krakow, Poland