Functional characteristics of neonatal rat β cells with distinct markers

J Mol Endocrinol. 2013 Dec 19;52(1):11-28. doi: 10.1530/JME-13-0106. Print 2014 Feb.


Neonatal β cells are considered developmentally immature and hence less glucose responsive. To study the acquisition of mature glucose responsiveness, we compared glucose-regulated redox state, insulin synthesis, and secretion of β cells purified from neonatal or 10-week-old rats with their transcriptomes and proteomes measured by oligonucleotide and LC-MS/MS profiling. Lower glucose responsiveness of neonatal β cells was explained by two distinct properties: higher activity at low glucose and lower activity at high glucose. Basal hyperactivity was associated with higher NAD(P)H, a higher fraction of neonatal β cells actively incorporating (3)H-tyrosine, and persistently increased insulin secretion below 5 mM glucose. Neonatal β cells lacked the steep glucose-responsive NAD(P)H rise between 5 and 10 mM glucose characteristic for adult β cells and accumulated less NAD(P)H at high glucose. They had twofold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal β cells at a developmental crossroad: they showed advanced endocrine differentiation when specifically analyzed for their mRNA/protein level of classical neuroendocrine markers. On the other hand, discrete neonatal β cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, delta-like 1 homolog (DLK1) was used to investigate whether neonatal β cells with basal hyperactivity corresponded to a more immature subset with high DLK1, but no association was found. In conclusion, the current study supports the importance of glycolytic NADH-shuttling in stimulus function coupling, presents basal hyperactivity as novel property of neonatal β cells, and provides potential markers to recognize intercellular developmental differences in the endocrine pancreas.

Keywords: gene expression; islet cells; microarray; neonatal; pancreatic β cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Biomarkers / metabolism
  • Cell Differentiation
  • Cluster Analysis
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Glucose / metabolism
  • Insulin / metabolism
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / metabolism
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Metabolomics
  • NAD / metabolism
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Oxidation-Reduction
  • Proteomics
  • Rats


  • Biomarkers
  • Dlk1 protein, rat
  • Insulin
  • Intercellular Signaling Peptides and Proteins
  • MafB Transcription Factor
  • Mafb protein, rat
  • Membrane Proteins
  • Oncogene Proteins
  • NAD
  • Glucose