The role of phosphodiesterase 3B in energy metabolism

Sammanfattning: Energy metabolism at the level of any particular tissue is tightly regulated by hormones, neurotransmitters and cytokines in order to maintain overall energy homeostasis. Any dysfunctions in energy metabolism may lead to more or less severe consequences, with obesity and type 2 diabetes being the most prevalent ones. Type 2 diabetes is characterized by defective insulin secretion (?-cell dysfunction) and action (insulin resistance). The cAMP-degrading enzyme, PDE3B mediates antilipolytic insulin action in adipocytes and antiglycogenolytic insulin action in hepatocytes. The aim of this work was to evaluate the role of PDE3B in overall energy homeostasis as well as in insulin-induced glucose uptake and lipogenesis in adipocytes. Furthermore, we investigated mechanisms whereby PDE3B could regulate energy metabolism as well as long-term regulation of the enzyme by insulin and catecholamines. Used models included PDE3B KO mice generated for the first time, primary adipocytes and cell lines. The results indicate that PDE3B plays unique roles in adipocytes, liver and pancreatic ?-cells, and is crucial for the regulation of overall energy metabolism. Furthermore, in adipocyes, PDE3B is involved in the regulation of insulin-induced glucose uptake and lipogenesis, presumably via regulation of cAMP/Epac signalling which has an impact on phosphorylation and activation of PKB and ACC. At last, in adipocytes PDE3B and PDE4 are regulated by insulin and catecholamines also on a long-term basis. Altered expression of adipocyte PDEs by insulin and catecholamines may contribute to altered regulation of metabolism in obesity and diabetic states.