When one becomes many-Alternative splicing in β-cell function and failure

Diabetes Obes Metab. 2018 Sep;20 Suppl 2(Suppl 2):77-87. doi: 10.1111/dom.13388.


Pancreatic β-cell dysfunction and death are determinant events in type 1 diabetes (T1D), but the molecular mechanisms behind β-cell fate remain poorly understood. Alternative splicing is a post-transcriptional mechanism by which a single gene generates different mRNA and protein isoforms, expanding the transcriptome complexity and enhancing protein diversity. Neuron-specific and certain serine/arginine-rich RNA binding proteins (RBP) are enriched in β-cells, playing crucial roles in the regulation of insulin secretion and β-cell survival. Moreover, alternative exon networks, regulated by inflammation or diabetes susceptibility genes, control key pathways and processes for the correct function and survival of β-cells. The challenge ahead of us is to understand the precise role of alternative splicing regulators and splice variants on β-cell function, dysfunction and death and develop tools to modulate it.

Keywords: alternative splicing; candidate genes; pancreatic β-cells; splicing factors; type 1 diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alternative Splicing / genetics
  • Alternative Splicing / physiology*
  • Autoimmunity / genetics
  • Autoimmunity / physiology
  • Base Sequence / genetics
  • Base Sequence / physiology
  • Cell Death / genetics
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 1 / prevention & control
  • Gene Expression / genetics
  • Humans
  • Insulin-Secreting Cells / physiology*
  • Neurons / metabolism
  • Phosphoproteins / genetics
  • RNA-Binding Proteins / physiology
  • Sequence Analysis, RNA
  • Serine-Arginine Splicing Factors / genetics


  • Phosphoproteins
  • RNA-Binding Proteins
  • SRSF6 protein, human
  • Serine-Arginine Splicing Factors