From PDE3B to the regulation of energy homeostasis

Curr Opin Pharmacol. 2011 Dec;11(6):676-82. doi: 10.1016/j.coph.2011.09.015. Epub 2011 Oct 14.


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.

Publication types

  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adipocytes, White / drug effects
  • Adipocytes, White / enzymology
  • Adipocytes, White / metabolism
  • Animals
  • Cyclic AMP / antagonists & inhibitors
  • Cyclic AMP / physiology
  • Cyclic GMP / antagonists & inhibitors
  • Cyclic GMP / physiology
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / chemistry
  • Cyclic Nucleotide Phosphodiesterases, Type 3 / metabolism*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / metabolism
  • Energy Intake* / drug effects
  • Energy Metabolism* / drug effects
  • Hepatocytes / drug effects
  • Hepatocytes / enzymology
  • Hepatocytes / metabolism
  • Humans
  • Molecular Targeted Therapy
  • Obesity / drug therapy
  • Obesity / enzymology
  • Obesity / metabolism
  • Phosphodiesterase 3 Inhibitors / pharmacology
  • Phosphodiesterase 3 Inhibitors / therapeutic use
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Second Messenger Systems* / drug effects


  • Phosphodiesterase 3 Inhibitors
  • Cyclic AMP
  • Cyclic Nucleotide Phosphodiesterases, Type 3
  • PDE3B protein, human
  • Cyclic GMP