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New Dimmer Switch For Controlling Insulin Production

Oct 9, 2015

Finding a new pathway to manage insulin production is a large step towards improving outcomes for patients with diabetes

It has been known that insulin secretion from beta cells of the pancreatic islets of Langerhans control metabolic homeostasis and is impaired in individuals with T2DM. In addition, research has found that another pathway exists to amplify secretory response. This pathway is likely at the distal exocytotic site, where the export of isocitrate from the mitochondria and interaction with cytosolic isocitrate dehydrogenase (ICDc) takes place. The exact mechanism for insulin secretion and its role in T2DM is unclear; however, it may be a key pathway.


Researcher Patrick E. MacDonald, PhD., who is an associate professor at the University of Alberta and a member of the Alberta Diabetes Institute, explains that completely understanding the islet cells in the pancreas that make insulin may lead new methods in treating, delaying, or preventing diabetes.

The new pathway to manage insulin production is considered a “dimmer switch” that can regulate the extent of insulin that is secreted as blood sugar rises and it can be restored by “turning on” the switch. During research, it was found that the glucose-dependent amplification of exocytosis was impaired in humans with T2DM (also in an in vitro model of human islet dysfunction). However, rescuing this dysfunction through signaling intermediates from the established pathway was recognized as a breakthrough finding.

Overall, researchers believe that fully understanding the mechanism of insulin production could lead to new ways in managing diabetes. In addition, researchers mention that there is not enough information available to halt T2DM yet. Nonetheless, this research is a large step towards understanding the initial stages of the development of diabetes.

Practice Pearls:

  • Export of isocitrate from the mitochondria and its interaction with cytosolic enzymes has an important role in insulin production, which requires more studies.
  • The new pathway for managing insulin production can regulate secretions through a “dimmer switch,” thereby, allowing better glucose control.
  • There is not enough data available to stop type 2 diabetes, but this study is a large step towards understanding where the error is occurring in the first place.

Ferdaoussi, Mourad, et al. “Isocitrate-to-SENP1 signaling amplifies insulin secretion and rescues dysfunctional β cells.” The Journal of clinical investigation 125.125 (10) (2015): 0-0.