Proteomics

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Functional characteristics of neonatal rat beta cells With distinct markers


ABSTRACT: 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 beta cells purified from neonatal or 10-weeks old rats to their transcriptomes and proteomes measured by oligonucleotide and LC-MS/MS profiling. Lower glucose-responsiveness of neonatal beta 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 beta cells actively incorporating 3H-Tyrosine, and persistently increased insulin secretion below 5 mM glucose. Neonatal beta cells lacked the steep glucose-responsive NAD(P)H rise between 5-10 mM glucose characteristic for adult beta cells, and accumulated less NAD(P)H at high glucose. They had 2-fold lower expression of malate/aspartate-NADH shuttle and most glycolytic enzymes. Genome-wide profiling situated neonatal beta 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 beta cell subpopulations still expressed mRNAs/proteins typical for developing/proliferating tissues. One example, Delta-like 1 homolog (DLK1) was used to investigate if neonatal beta 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 beta cells, and provides potential markers to recognize intercellular developmental differences in the endocrine pancreas.

INSTRUMENT(S): Synapt G2 MS

ORGANISM(S): Rattus norvegicus  

TISSUE(S): Pancreas

DISEASE(S): Not Available

SUBMITTER: Gertjan Kramer  

LAB HEAD: J.M.F.G Aerts

PROVIDER: PXD001577 | Pride | 2014-12-12

REPOSITORIES: Pride

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Functional characteristics of neonatal rat β cells with distinct markers.

Martens G A GA   Motté E E   Kramer G G   Stangé G G   Gaarn L W LW   Hellemans K K   Nielsen J H JH   Aerts J M JM   Ling Z Z   Pipeleers D D  

Journal of molecular endocrinology 20131219 1


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 l  ...[more]

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