It is known that cardiac natriuretic peptides (NPs) are hormones produced by the heart to influence blood pressure. When the heart senses elevated pressure, it releases NPs, which go to the kidneys, triggering the body to release salt and water from the bloodstream to lower blood pressure. NPs prompt the response to blood pressure by signaling through an active receptor, and are removed from the blood by a clearance receptor, with both receptors contributing to the level of NP activity.
Now, a study from researchers at the Sanford Burnham Prebys Medical Discovery Institute (SBP) has shown an important relationship between NPs and obesity, glucose intolerance, and insulin resistance. The team state that their findings offer a new approach to treating metabolic disorders by targeting the pathway that controls the proteins’ concentration in the blood. The opensource study is published in the journal Obesity.
Previous studies unexpectedly found NP receptors in human adipose tissue, suggesting that NP levels may play an additional role in metabolism and obesity. Indeed, subsequent studies have shown that circulating NP levels are lower in obese individuals and those with metabolic risk factors, including high glucose levels. More recently, research has shown that obese individuals have higher levels of the clearance receptor in adipose tissue. The current study illustrates how the regulation of NPs is altered in obesity, insulin resistance, and type 2 diabetes.
The current study examined levels of NP active receptor (NPRA) and NP clearance receptor (NPRC) in adipose and skeletal tissue in individuals with either obesity, insulin resistance, or type 2 diabetes. Results show higher levels of the receptor that clears NPs from circulation. The lab state that this suggests if NP levels can be boosted and/or the level of its clearance receptor reduced, they may be able to correct some of these conditions. Data findings show that higher BMI values are associated with elevated levels of the clearance receptor in adipose tissue.
The group then looked at NP receptor levels in patients with type 2 diabetes after taking pioglitazone, a drug used to improve insulin sensitivity and control blood sugar in diabetic patients. Results show that these patients had a significant reduction in the level of the clearance receptor in adipose tissue, further reinforcing the link between NPs, insulin resistance, and obesity.
The team surmise that their results suggest that drugs that target the pathways which lead to increased NP levels may be a new way to treat metabolic disorders, such as obesity, insulin resistance, and type 2 diabetes. For the future, the researchers state that as there are FDA-approved drugs to control blood sugar which also impact NP levels, they may be able to redesign these drugs to specifically target other metabolic conditions.