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The RNA-binding protein LARP1 is dispensable for pancreatic β-cell function and mass

Joao Pedro Werneck-de-Castro1,2, Flavia Leticia Martins Peçanha1, Diego Henrique Silvestre3

  • 1Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.

Scientific Reports
|January 23, 2021
PubMed

Insights

Mechanistic target of rapamycin complex 1 (mTORC1) regulates translation. La-related protein 1 (LARP1) is highly expressed in pancreatic beta cells and upregulated in diabetes, but its deletion did not affect glucose homeostasis.

Area of Science:

  • Cellular and Molecular Biology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Mechanistic target of rapamycin complex 1 (mTORC1) dysregulation in pancreatic beta cells is linked to diabetes.
  • mTORC1 interacts with La-related protein 1 (LARP1) to control 5' terminal oligopyrimidine tract (5'TOP) mRNA expression, crucial for translation and ribosome biogenesis.

Purpose of the Study:

  • To investigate the role of LARP1 in pancreatic beta cells and its potential involvement in diabetes.
  • To determine if LARP1 expression levels correlate with diabetic conditions.

Main Methods:

  • Quantified LARP1 and LARP1B expression in mouse islets and human beta cells.
  • Analyzed beta-cell specific Larp1 knockout (β-Larp1KO) mice under basal and diabetogenic conditions (high-fat and high-branched-chain amino acid diets).
  • Assessed insulin secretion, glucose metabolism, glycemia, and beta-cell mass.

Main Results:

  • LARP1 is the predominant LARP family member in mouse islets and human beta cells.
  • LARP1 and LARP1B expression are elevated in beta cells from diabetic patients.
  • β-Larp1KO mice exhibited no significant impairment in insulin secretion or glucose homeostasis under basal or diet-induced stress, except for a minor glucose intolerance at 16 weeks on a BCAA diet.

Conclusions:

  • LARP1 is highly expressed in beta cells and upregulated in diabetes, but its genetic disruption does not significantly impact glucose homeostasis.
  • LARP1 may not play a major role in beta cell function or diabetes pathogenesis.
  • Further research may be needed to fully elucidate the role of LARP1 in metabolic regulation.

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