A target for identifying and treating metabolic diseases including insulin resistance

Unmet Need

The World Health Organization attributes over 70% of all deaths globally to noncommunicable diseases (NCD) including cardiovascular disease, diabetes, and cancer. Risk factors for NCDs include obesity, raised blood pressure, and the regional distribution of lipid deposited within the adipose tissue. However, researchers don’t fully understand what causes NCDs, such as insulin resistance and prediabetes that eventually lead to the over 30 million Americans with type 2 diabetes. There is a need for better management of NCDs, including screening, detecting, and treating these diseases.

Technology

Duke inventors have reported a method for identifying and treating metabolic dysfunction, such as insulin resistance. Specifically, they have shown that PLEXIN D1 (PLXND1) regulates body fat distribution and insulin sensitivity. The inventors used genetic analysis and in vivo imaging of lipid deposition dynamics in zebrafish to assess the role of PLXND1 in adipose tissue morphology and fat distribution. In addition to zebrafish studies, they have also conducted molecular and physiological assessments in humans that support a conserved role for PLXND1 in regulation of visceral adipose tissue morphology and insulin sensitivity.

Advantages

  • Offers therapeutic, prognostic, and diagnostic applications for metabolic diseases
  • Demonstrated high-fat-induced insulin resistance in PLXND1-deficient zebrafish
  • Human PLXND1 mRNA was positively associated with type 2 diabetes, supporting the applicability of this technology to patients
  • Particularly relevant to regional adiposity (i.e., visceral vs subcutaneous adipose tissue distribution) which has distinct associations with metabolic health and distinct genetic contributions, as compared with more general measures of adiposity