From PDE3B to the regulation of energy homeostasis

The incidence of obesity in the developed world is increasing at an alarming rate. Concurrent with the increase in the incidence of obesity is an increase in the incidence of type 2 diabetes. Cyclic AMP (cAMP) and cGMP are key second messengers in all cells; for example, when it comes to processes of relevance for the regulation of energy metabolism, cAMP is a key mediator in the regulation of lipolysis, glycogenolysis, gluconeogenesis and pancreatic β cell insulin secretion. PDE3B, one of several enzymes which hydrolyze cAMP and cGMP, is expressed in cells of importance for the regulation of energy homeostasis, including adipocytes, hepatocytes, hypothalamic cells and β cells. It has been shown, using PDE3 inhibitors and gene targeting approaches in cells and animals, that altered levels of PDE3B result in a number of changes in the regulation of glucose and lipid metabolism and in overall energy homeostasis. This article highlights the complexity involved in the regulation of PDE3B by hormones, and in the regulation of downstream metabolic effects by PDE3B in several interacting tissues.

► Acute hormonal regulation of PDE3B involves reversible protein phosphorylation and protein complex formation at different subcellular locations.
► PDE3B plays a key role in the regulation of adipocyte lipolysis.
► PDE3B plays a key role in the regulation of insulin secretion.
► PDE3B plays an important role in overall energy homeostasis.
► PDE3B is downregulated in adipose tissue in human obesity.