June 22, 2011 A new signal pathway that renders the insulin-releasing beta cell more sensitive to high levels of blood glucose has been discovered by researchers at the Swedish medical university Karolinska Institutet. A second new study reveals a possible way to delay the disease by inhibiting a lipoprotein.
A new joint study published in Nature Medicine and conducted by researchers at Karolinska Institutet's Department of Molecular Medicine and Surgery and their American colleagues provides new insights into how beta cells react to raised concentrations of blood sugar, which occur, for example, after a meal.
The study focuses on acetylcholine, a key neurotransmitter in beta cell function. Although the substance is released by neurons in mice, the human mechanism is unclear. These new results show that acetylcholine in the human pancreas is produced by alpha cells, which also produce glucagon, the hormone that raises blood sugar levels.
"The fact that acetylcholine has a central part to play in the effective secretion of insulin in response to an increase in blood sugar levels and that we now understand how this substance is released by the human pancreas makes this signal pathway very interesting from a treatment perspective," says principal investigator Professor Per-Olof Berggren.
A second study, published recently in the Proceedings of the National Academy of Sciences and also conducted by researchers at Karolinska Institutet's Department of Molecular Medicine and Surgery, presents a possible method of delaying the disease.
Type I diabetes coincides with high blood concentrations of the lipoprotein apolipoprotein CIII (ApoCIII). The team has now demonstrated on rats, which develop a form of type I diabetes analogous to the human kind, that levels of Apo CIII are raised before the onset of the disease and that this causes the insulin producing beta cells to die.
By reducing the production of ApoCIII using antisense therapy, the researchers succeeded in significantly delaying the onset of diabetes to the extent that it took twice as long for the rats to develop the disease.
The team concludes that a rise in ApoCIII levels is a significant diabetes precursor. It is now hoped that the onset of the disease can be delayed in individuals in the risk-zone for type I diabetes by reducing the concentration of ApoCIII in their blood.
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- Rayner Rodriguez-Diaz, Robin Dando, M Caroline Jacques-Silva, Alberto Fachado, Judith Molina, Midhat H Abdulreda, Camillo Ricordi, Stephen D Roper, Per-Olof Berggren, Alejandro Caicedo. Alpha cells secrete acetylcholine as a non-neuronal paracrine signal priming beta cell function in humans. Nature Medicine, 2011; DOI: 10.1038/nm.2371
- R. Holmberg, E. Refai, A. Hoog, R. M. Crooke, M. Graham, G. Olivecrona, P.-O. Berggren, L. Juntti-Berggren. Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proceedings of the National Academy of Sciences, 2011; DOI: 10.1073/pnas.1019553108
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