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Jens Lagerstedt

Associate professor

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Secretory granule exocytosis and its amplification by cAMP in pancreatic β-cells

Author

  • Mototsugu Nagao
  • Jens O. Lagerstedt
  • Lena Eliasson

Summary, in English

The sequence of events for secreting insulin in response to glucose in pancreatic β-cells is termed “stimulus-secretion coupling”. The core of stimulus-secretion coupling is a process which generates electrical activity in response to glucose uptake and causes Ca2+ oscillation for triggering exocytosis of insulin-containing secretory granules. Prior to exocytosis, the secretory granules are mobilized and docked to the plasma membrane and primed for fusion with the plasma membrane. Together with the final fusion with the plasma membrane, these steps are named the exocytosis process of insulin secretion. The steps involved in the exocytosis process are crucial for insulin release from β-cells and considered indispensable for glucose homeostasis. We recently confirmed a signature of defective exocytosis process in human islets and β-cells of obese donors with type 2 diabetes (T2D). Furthermore, cyclic AMP (cAMP) potentiates glucose-stimulated insulin secretion through mechanisms including accelerating the exocytosis process. In this mini-review, we aimed to organize essential knowledge of the secretory granule exocytosis and its amplification by cAMP. Then, we suggest the fatty acid translocase CD36 as a predisposition in β-cells for causing defective exocytosis, which is considered a pathogenesis of T2D in relation to obesity. Finally, we propose potential therapeutics of the defective exocytosis based on a CD36-neutralizing antibody and on Apolipoprotein A-I (ApoA-I), for improving β-cell function in T2D.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Medical Protein Science
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2022

Language

English

Publication/Series

Diabetology International

Document type

Journal article review

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Apolipoprotein A-I
  • CD36
  • Diabetes
  • Exocytosis
  • Insulin secretion
  • Type 2 diabetes
  • β-Cell

Status

Epub

Research group

  • Diabetes - Islet Cell Exocytosis
  • Medical Protein Science

ISBN/ISSN/Other

  • ISSN: 2190-1678