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Alpha Beta Crosstalk: Beta to Alpha Cells and Back!

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Dr Madhukar Mittal, Jodhpur, Rajasthan    27 November 2019

  • Biological crosstalk – Components of one signal transduction pathway affect another in a number of ways, most common form being crosstalk between proteins of signaling cascades.
  • There is a crosstalk between cells that control body’s response to sugar and understanding the conversation can help us understand and treat diabetes.
  • In type 1 diabetes mellitus, there is almost complete destruction of b-cells; a-cells are present but their function is impaired. In type 2 diabetes mellitus, b-cell number reduction is progressive and a-cell numbers may actually be increased.
  • Artemisinins inhibit ARX function and impair a-cell identity. Artemisinins increase b-cell mass in zebrafish and rodent models. They target GABAA receptor signaling.
  • Glucagon-like peptide-1 (GLP-1) receptor agonists exert some of their glycemic effects through reduction in endogenous glucagon. GLP-1 treatment reduces glucagon secretion: by action on pancreatic a-cells, and by stimulation of b-cells, and the paracrine effects of the secreted insulin on adjacent a-cells.
  • There are significant structural and functional differences in rodent islets and human islets.
  • Structure of human islets permits greater role of paracrine and autocrine interactions in regulating islet cell function.
  • This is an ever-expanding area of research with knowledge gaps, and has a potential role in the management of diabetes.

Deciphering a-b crosstalk has potential for curative therapies for diabetes.

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