Signal transduction between the diabetogenic blood factor apolipoprotein CIII (apoCIII) and insulin-producing beta cells is now clarified. ApoCIII acts upon the calcium channels through kinases PKA and Src, involving a receptor SR-BI and an integrin beta1. The results are published in Cellular and Molecular Life Sciences on the 15th of August 2013.
Calcium is very important for a normal function of insulin-secreting beta-cells. Calcium is transported into the and out of the cells via calcium channels. Serum factor apoCIII has been identified as a cause for increased activity of these channels, leading to higher concentration of calcium and subsequently beta-cell death. So far, the signal transduction mechanism of this action has remained unknown.
Researchers in Professor P-O Berggren’s group at Karolinska Institutet have now clarified the signal transduction pathway. A joint action of beta1 integrin and SR-BI receptors, sitting in the beta-cell membrane, is needed to convey the apoCIII stimulation to the PKA and Prs kinases. A parallel activation of these kinases inside the beta cell keeps the calcium channels open and functional for a longer time.
Discovery of this molecular pathway opens opportunities for development of novel drugs for prevention of beta-cell death and development of diabetes. The results are published in Cellular and Molecular Life Sciences on the 15th of August 2013.
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