A beneficial role of GLP-1 receptor agonist therapy in ABCC8-MODY (MODY 12)

J Diabetes Complications. 2023 Sep;37(9):108566. doi: 10.1016/j.jdiacomp.2023.108566. Epub 2023 Jul 28.

Abstract

Maturity-onset diabetes of the young (MODY) is an inherited form of diabetes resulting from a mutation in a single gene. ABCC8-MODY is caused by mutations in the ABCC8 gene, which encodes sulfonylurea receptor 1 (SUR1), a regulatory component of the ATP-sensitive potassium (KATP) channel found in beta cells. In ABCC8-MODY, mutations in the ABCC8 gene interfere with insulin secretion in response to glucose. Recent evidence suggests that therapy with GLP-1 receptor agonists (GLP-1 RAs) may be beneficial in ABCC8-MODY. This report presents a successful treatment of a 49-year-old woman diagnosed with ABCC8-MODY using the GLP-1 RA semaglutide. The patient, who had been previously receiving insulin therapy, experienced significant improvements in glycemic control and weight loss after transitioning to semaglutide. GLP-1 RAs potentially enhance insulin secretion in ABCC8-MODY by activating multiple signaling pathways involved in insulin secretion. The report highlights the potential of GLP-1 RA therapy as an alternative to sulfonylureas and insulin for individuals with ABCC8-MODY. GLP-1 RAs have previously demonstrated benefits in other forms of MODY. Understanding the molecular mechanisms through which GLP-1 RAs promote insulin secretion, including their effects on KATP channels and activation of PKA and Epac signaling, offers valuable insights into their therapeutic effects.

Keywords: ABCC8-MODY; GLP-1 receptor agonist; K(ATP) channel.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Triphosphate / therapeutic use
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / genetics
  • Female
  • Glucagon-Like Peptide-1 Receptor / metabolism
  • Humans
  • Insulin / metabolism
  • Insulin / therapeutic use
  • Middle Aged
  • Potassium Channels, Inwardly Rectifying* / genetics
  • Sulfonylurea Receptors / genetics
  • Transcription Factors / metabolism

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Potassium Channels, Inwardly Rectifying
  • Insulin
  • Transcription Factors
  • Adenosine Triphosphate
  • ABCC8 protein, human
  • Sulfonylurea Receptors

Supplementary concepts

  • Mason-Type Diabetes