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Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors01:28

Treatment for Pulmonary Arterial Hypertension: Phosphodiesterase Inhibitors

Phosphodiesterase 5 (PDE5) inhibitors are potent enzymes that function to hydrolyze cyclic nucleotides to their corresponding 5' monophosphates. Their unique biochemical properties have been applied in treating Pulmonary Arterial Hypertension (PAH).
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GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

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Two...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

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Related Experiment Video

Updated: Jun 13, 2026

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

Sildenafil promotes adipogenesis through a PKG pathway.

Xiaodong Zhang1, Jun Ji, Guirui Yan

  • 1Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.

Biochemical and Biophysical Research Communications
|May 18, 2010
PubMed
Summary

Sildenafil, a PDE5 inhibitor, promotes adipogenesis and glucose uptake in cells. This effect is mediated by the PKG pathway, suggesting a novel role for PDE5 inhibitors beyond their known applications.

Related Experiment Videos

Last Updated: Jun 13, 2026

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro
09:41

Measuring the Rate of Lipolysis in Ex Vivo Murine Adipose Tissue and Primary Preadipocytes Differentiated In Vitro

Published on: March 17, 2023

Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Sildenafil is an established oral phosphodiesterase type 5 (PDE5) inhibitor.
  • PDE5 inhibitors are primarily used for treating erectile dysfunction and pulmonary arterial hypertension.
  • The role of PDE5 inhibitors in cellular processes like adipogenesis is not well-understood.

Purpose of the Study:

  • To investigate the effect of sildenafil on adipogenesis in 3T3L1 preadipocytes.
  • To explore the underlying molecular mechanisms, including gene expression and signaling pathways.
  • To determine if other PDE5 inhibitors or cGMP analogs share similar effects.

Main Methods:

  • Treatment of 3T3-L1 preadipocytes with sildenafil and other PDE5 inhibitors.
  • Assessment of adipogenesis through lipid droplet and triglyceride content analysis.
  • Analysis of adipocyte-specific gene expression using RT-PCR and Western blotting.
  • Investigation of the involvement of the PKG pathway using specific inhibitors and cGMP analogs.

Main Results:

  • Sildenafil significantly promoted adipogenesis and increased lipid accumulation in 3T3-L1 cells.
  • Sildenafil upregulated key adipogenic genes, including aP2, GLUT4, C/EBP beta, PPAR gamma, and C/EBP alpha.
  • Other PDE5 inhibitors and a cGMP analog also enhanced adipogenesis, indicating a conserved mechanism.
  • The PKG inhibitor Rp-8-pCPT-cGMP blocked sildenafil- and cGMP-induced adipogenesis.
  • Sildenafil enhanced glucose uptake, an effect also inhibited by Rp-8-pCPT-cGMP.

Conclusions:

  • Sildenafil promotes adipogenesis and glucose uptake in 3T3-L1 cells.
  • The mechanism involves the activation of the protein kinase G (PKG) pathway.
  • These findings suggest a potential role for PDE5 inhibitors in metabolic regulation.