d-Amino Acids and Classical Neurotransmitters in Healthy and Type 2 Diabetes-Affected Human Pancreatic Islets of Langerhans

Cindy J. Lee, Jack H. Schnieders, Stanislav S. Rubakhin, Amit V. Patel, Chengyang Liu, Ali Naji, Jonathan V. Sweedler

Research output: Contribution to journalArticlepeer-review


The pancreatic islets of Langerhans are clusters of cells that function as endocrine units synthesizing and releasing insulin and a range of additional peptide hormones. The structural and chemical characteristics of islets change during type 2 diabetes development. Although a range of metabolites including neurotransmitters has been reported in rodent islets, the involvement of these cell-to-cell signaling molecules within human pancreatic islets in the pathophysiology of type 2 diabetes is not well known, despite studies suggesting that these molecules impact intra- and inter-islet signaling pathways. We characterize the enigmatic cell-to-cell signaling molecules, d-serine (d-Ser) and d-aspartate (d-Asp), along with multiple classical neurotransmitters and related molecules, in healthy versus type 2 diabetes-affected human islets using capillary electrophoresis separations. Significantly reduced d-Ser percentage and gamma-aminobutyric acid (GABA) levels were found in type 2 diabetes-affected islets compared to healthy islets. In addition, the negative correlations of many of the signaling molecules, such as d-Ser percentage (r = −0.35), d-Asp (r = −0.32), serotonin (r = −0.42), and GABA (r = −0.39) levels, with hemoglobin A1c (HbA1c) levels and thus with the progression of type 2 diabetes further demonstrate the disruption in intra- or inter-islet signaling pathways and suggest that these cell-to-cell signaling molecules may be potential therapeutic targets.

Original languageEnglish (US)
Article number799
Issue number9
StatePublished - Sep 2022


  • d-amino acids
  • mass spectrometry
  • laser-induced fluorescence
  • chiral analysis
  • diabetes
  • endocrine system
  • pancreatic islet
  • cell signaling
  • neurotransmitter
  • amino acid

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology


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