Calcium: Good for Your Bones and Your Beta Cells

Calcium: Good for Your Bones and Your Beta Cells

By: Alex Parrott

Everyone knows calcium is great for bones, but new findings are showing that calcium2+(Ca2+)   can be more useful for treating diabetes than previously thought. There is still a lot of research to be done, but each of Dr. Su’s, Dr. Klec’s and Dr. Verma’s teams have given great views and reasoning as to why Ca2+ signaling, mitochondria associated membranes (MAMS), and prohibitin (PHB), may be the next breakthrough for understanding the physiology of beta cell and other organelle’s dysfunctions associated with diabetes. 

While the importance of Ca2+ in insulin release is well documented, not much is known about how it interacts with the mitochondria and PHB. When cells sense there is a rise in blood glucose, they use that glucose to fuel mitochondria so that the plasma membrane can be depolarized, in turn allowing Ca2+  to enter the cells. Once it enters, the waves of Ca2+ trigger the secretory granules to release the insulin they contain, which levels out the glucose levels. 

These large concentrations of Ca2+ affect other processes as well. Dr. Verma mentions in his review that mitochondria and Ca2+ play a major role in beta cell depth due to the unmanaged concentrations of Ca2+ in the endoplasmic reticulum (ER). The Ca2+ sourced apoptosis is linked to the mitochondrial dysfunction through prohibitin (PHB). Dysfunction of PHB, a mitochondrial scaffold protein, causes mitochondrial dysfunction that leads to diseases like diabetes. 

But how does the ER Ca2+ signaling affect PHB in mitochondria?

The answer:MAMs. These two organelles talk through mitochondria associated membranes. These connections are vital for many functions such as calcium signaling, cell survival and homeostasis in cellular metabolism. Dr. Su’s review suggests that the dysfunction of the organelles and the MAMs are what’s causing the beta cell death by establishing apoptotic pathways. 

So, what does all this mean?

Well, not enough research has been done to draw a conclusion yet, but these hypotheses and reviews all point to these three areas as a big research focus moving forward. Perhaps one way of understanding these intricate insulin secretion processes could be through the study of synthetic beta cells, which might help scientists understand Ca2+ mechanics,which in turn could be a major contributor in understanding the development and identification of the onset of diabetes. Additionally, if the PHB and Ca2+ connections are studied more, they could lead to the development of target drugs that identify these pathways and enable treatment of the stress-induced dysfunction of the beta cells, as well as prevent the deterioration of the beta cell mass. Similarly, future studies of MAM dysfunction can also lead to strategies of treating dysfunctional beta cells and insulin resistance. 

Sources 

  • Klec, Christiane, et al. “Calcium Signaling in ß-Cell Physiology and Pathology: A Revisit.” International Journal of Molecular Sciences, MDPI, 4 Dec. 2019, www.ncbi.nlm.nih.gov/pmc/articles/PMC6940736/. 
  • Merkwirth, Carsten, and Thomas Langer. “Prohibitin Function within Mitochondria: Essential Roles for Cell Proliferation and Cristae Morphogenesis.” Biochimica Et Biophysica Acta (BBA) – Molecular Cell Research, Elsevier, 30 May 2008, www.sciencedirect.com/science/article/pii/S0167488908001961. 
  • Verma, Gaurav, et al. “A Putative Prohibitin-Calcium Nexus in β-Cell Mitochondria and Diabetes.” Journal of Diabetes Research, Hindawi, 8 Oct. 2020, www.hindawi.com/journals/jdr/2020/7814628/. 
  • Yang, Shanshan, et al. “Mitochondria-Associated Endoplasmic Reticulum Membranes in the Pathogenesis of Type 2 Diabetes Mellitus.” Frontiers, Frontiers, 21 Aug. 2020, www.frontiersin.org/articles/10.3389/fcell.2020.571554/full. 

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