Journal
JOURNAL OF MOLECULAR ENDOCRINOLOGY
Volume 52, Issue 1, Pages 11-28Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JME-13-0106
Keywords
islet cells; microarray; neonatal; pancreatic beta cell; gene expression
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Funding
- Research Foundation Flanders [FWO G.0428.09N]
- Research Foundation Flanders (FWO) [G.0492.12N]
- European Foundation for the Study of Diabetes
- European Union [241883]
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Neonatal beta 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 b 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 b 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 b cells actively incorporating 3 H-tyrosine, and persistently increased insulin secretion below 5 mMglucose. Neonatal b cells lacked the steep glucose-responsive NAD(P) H rise between 5 and 10 mM glucose characteristic for adult b 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 b 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 b cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, delta-like 1 homolog (DLK1) was used to investigate whether neonatal b 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 b cells, and provides potential markers to recognize intercellular developmental differences in the endocrine pancreas.
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