PDE3B in Metabolic Regulation

Phosphodiesterase 3B (PDE3B) is a protein that plays a role in how cells handle nutrients (i.e. glucose and fats). The investigators have recently found that people who have a gene variant (i.e., change in the DNA) that reduces the function of the PDE3B protein may be protected from the development of diabetes and heart disease. However, it is unclear how this happens.

The aims of this study are to examine:

• What is the role of PDE3B in fat tissue function?
• How does PDE3B influence the way one's body handles blood sugars and lipids?

To this end, the investigators propose to study people who have a variant that reduces the function of that PDE3B and an equal number of people with the typical genotype.

Participants will be asked to attend two visits:

• a 4-h screening visit: involving a medical examination, blood tests before/after drinking a sugary drink and assessment of lifestyle (physical activity/sleep/diet) using questionnaires and smartwatch.
• a 24-h metabolic testing visit (only for eligible participants): involving an infusion of insulin and collection of blood samples and fat tissue from the lower tummy.

These investigations will provide a great opportunity to study how people with or without the variant handle fat, sugars and lipids in their bodies. They will also help the scientific community to understand the role of PDE3B in humans and possibly develop new ways to prevent or fight conditions like diabetes and heart disease.

Inclusion criteria

• willing and able to give informed consent for participation in the study
• aged 21-75 years
• men and women

Exclusion criteria

• unstable weight (>5% change the last 2 months)
• type 2 diabetes or other major organ dysfunction
• cancer in last 5 years
• gastrointestinal or bariatric surgery (except cholecystectomy and appendectomy)
• conditions that render subject unable to complete all testing procedures (including individuals with known allergies or contraindications to the medications used in this study)
• use of medications that affect the study outcome measures or increase the risk of study procedures and that cannot be temporarily discontinued
• smoking
• illegal drug use
• pregnant or lactating
• unable to grant voluntary informed consent or comply with the study instructions