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PDE12 in type 1 diabetes

Hasim Tekin1, Knud Josefsen1, Lars Krogvold2,3

  • 1The Bartholin Institute, Department of Pathology, Rigshospitalet, Copenhagen Biocenter, Ole Maaløes Vej 5, 2200, Copenhagen N, Denmark.

Scientific Reports
|October 28, 2022
PubMed

Insights

COVID-19 infection may increase type 1 diabetes (T1D) risk in children. Reduced PDE12 expression, a regulator of RNAseL, is linked to T1D and may be influenced by viral infections, potentially explaining the T1D incidence rise.

Area of Science:

  • Immunology
  • Virology
  • Endocrinology

Background:

  • Type 1 diabetes (T1D) incidence is rising, particularly in children, with a notable increase observed post-COVID-19 infection.
  • The interferon-α-activated RNAseL pathway degrades pathogen RNA but can harm host RNA if poorly regulated.
  • PDE12 regulates RNAseL activity by degrading 2'-5' oligoadenylate units.

Purpose of the Study:

  • To investigate the role of PDE12 expression and its genetic variations in Type 1 Diabetes (T1D).
  • To explore the potential link between decreased PDE12 expression, COVID-19 infection, and the increased incidence of T1D.

Main Methods:

  • Analyzed PDE12 gene expression in pancreatic islets from non-diabetic, T1D (newly and recently diagnosed), and T2D individuals.
  • Examined PDE12 single-nucleotide polymorphisms (SNPs) in relation to T1D incidence.
  • Compared PDE12 expression and SNP data between diabetic and non-diabetic cohorts.

Main Results:

  • PDE12 expression was significantly decreased in recently diagnosed T1D patients and in some newly diagnosed T1D patients.
  • No significant changes in PDE12 expression were observed in Type 2 Diabetes (T2D) patients.
  • Two rare PDE12 SNPs were associated with an increased odds ratio for T1D development (1.80 and 1.74).

Conclusions:

  • Reduced PDE12 expression in pancreatic islets is associated with Type 1 Diabetes (T1D), particularly in recently diagnosed individuals.
  • Specific PDE12 genetic variations may confer an increased susceptibility to T1D.
  • The findings suggest that decreased PDE12 expression, potentially exacerbated by viral infections like COVID-19, could contribute to the observed rise in T1D incidence.

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