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Low-protein diet disrupts the crosstalk between the PKA and PKC signaling pathways in isolated pancreatic islets

Bruno Rodrigo da Silva Lippo1, Thiago Martins Batista2, Luiz Fernando de Rezende2

  • 1Department of Pharmaceutical Sciences, Federal University of Pernambuco, 50740-600, Recife, PE, Brazil.

The Journal of Nutritional Biochemistry
|March 5, 2015
PubMed

Insights

Early-life protein restriction impairs pancreatic islet function by disrupting signaling pathways. This affects insulin secretion synergism between cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) and protein kinase C (PKC).

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Nutritional Science

Background:

  • Early-life protein restriction is known to affect pancreatic function, including reduced insulin secretion and intracellular calcium levels.
  • The precise molecular mechanisms underlying these alterations, particularly concerning glucose-stimulated insulin secretion pathways, remain incompletely understood.

Purpose of the Study:

  • To investigate the impact of early-life protein restriction on the signaling pathways that potentiate insulin secretion.
  • To elucidate how protein restriction affects the interplay between cAMP-dependent protein kinase (PKA) and Ca(2+)-dependent protein kinase C (PKC) in pancreatic islets.

Main Methods:

  • Isolated pancreatic islets from rats fed a low-protein (LP) diet were used.
  • Western blot analysis was performed to assess protein phosphorylation levels, including phospho-CREB and PKC substrates.
  • Cyclic adenosine monophosphate (cAMP) levels and global calcium (Ca(2+)) entry were measured.

Main Results:

  • Protein restriction disrupted the synergistic interaction between PKA and PKC in insulin secretion.
  • LP islets showed reduced levels of phospho-CREB and Phospho-(Ser) PKC substrate, indicating impaired PKA and PKC activity.
  • Reduced cAMP levels and global Ca(2+) entry were observed in LP islets.

Conclusions:

  • Early-life protein restriction alters the crosstalk between PKA and PKC signaling pathways in pancreatic islets.
  • This disruption in signaling crosstalk leads to impaired secretory synergism, contributing to altered insulin secretion.
Keywords:
CrosstalkInsulin secretionLow-protein dietPKAPKC

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