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Upcoming: Targeting Inceptor for Diabetes Therapy

By Lourdes Cross posted 21 days ago

  

Upcoming: Targeting Inceptor for Diabetes Therapy

Payton Waltz, PharmD
PGY1 Pharmacy Resident
Sullivan University College of Pharmacy and Health Sciences, Louisville, KY

Welcome to the celebration for the 100th year of insulin therapy! In 1921, Frederick Banting, Charles Best, and John MacLeod all played a hand at discovering the use of insulin therapy in patients with diabetes.1 According to the National Diabetes Statistics Report of 2020, 10.5% of the U.S. population had diabetes and 34.5% were classified as patients with prediabetes.2 This disease, affecting the insulin-producing islet cells of the pancreas, impacts a large percentage of this country’s population and will likely continue to increase. When insulin was discovered in 1921, it was known that insulin was a therapy to treat the symptoms of diabetes but not a treatment to cure.3 Over the last 100 years, no evidence has shown otherwise. Additionally, current diabetes therapy has yet to show evidence of reversing or stopping progression of the disease. A research group at Helmholtz Zentrum München in Germany has been researching potential regenerative treatments and recently discovered the insulin inhibitory receptor (nicknamed “inceptor”).

The function of inceptor is to block beta cells from insulin pathway initiation.3 This is thought to play a role in insulin resistance due to the inhibition of insulin signaling and upregulation of inceptor in diabetes. It is anticipated that blocking inceptor will assist with beta cell regeneration without the weight gain commonly associated with insulin use. 

The discovery of the insulin inhibitory receptor was thanks to knockout mice that lacked inceptor and portrayed signs of hypoglycemia and hyperinsulinemia.4 To add credit to this finding, inceptor negative mice had lower fasting blood glucose levels 2 to 5 hours after birth than inceptor positive mice and 50% of inceptor negative mice could be saved with glucagon injections. The lack of inceptor also showed increased beta cell proliferation during the formation of the pancreas and affected glucose equilibrium after birth.

After many studies involving co-immunoprecipitation, the study of protein-protein interactions in vivo, these researchers found that inceptor desensitizes insulin sensitivity receptor and insulin-like growth factor 1 via clathrin-mediated endocytosis in the pancreas. Thus, it exposes a target to increase the functional beta cell mass.4

If a drug can be found to inhibit inceptor in humans causing a sensitization of insulin sensitivity factor and insulin-like growth factor 1, patients could have an improved response to their own production of insulin and diabetes medications. This potential to enhance pancreatic beta cells could allow for regeneration and remission of patients with diabetes across the world.

References  

  1. Felman A. Who discovered insulin? Medical News Today. November 23, 2018. Accessed July 10, https://www.medicalnewstoday.com/articles/323774#summary.
  2. National Diabetes Statistics Report, 2020. Centers for Disease Control and Prevention. August 28, 2020; Accessed July 10,2021. https://www.cdc.gov/diabetes/data/statistics-report/index.html.
  3. Scientists discover a new promising target for diabetes treatment. ScienceDaily. January 27 2021; Accessed July 10, 2021. https://www.sciencedaily.com/releases/2021/01/210127122356.htm.
  4. Ansarullah, Jain C, Far FF, et al. Inceptor counteracts insulin signaling in β-cells to control glycaemia. 2021;590:326-331. https://doi.org/10.1038/s41586-021-03225-8.
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