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Related Concept Videos

Cells and Secretions of the Pancreas01:16

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The pancreas, a vital organ within the abdominal cavity, plays dual roles in the digestive and endocrine systems, collaborating with exocrine and endocrine cells to maintain optimal digestion and blood sugar levels.
Exocrine function is carried out by acinar cells, organized into clusters known as acini. These cells contribute to digestion by releasing substantial quantities of enzyme-rich, alkaline digestive juices.
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The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
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KSRP improves pancreatic beta cell function and survival.

Leticia Barssotti1, Gabriela Moreira Soares1, Emílio Marconato-Júnior1

  • 1Obesity and Comorbidities Research Center (OCRC), Department of Structural and Functional Biology, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, 13083864, Brazil.

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|March 14, 2024
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Summary

KH-type splicing regulatory protein (KSRP) is crucial for pancreatic beta cell health. Reduced KSRP levels worsen beta cell dysfunction and insulin secretion, suggesting KSRP as a therapeutic target for type 2 diabetes.

Keywords:
Cell deathER stressInsulin secretionKSRPPancreatic beta cell

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Area of Science:

  • Cell Biology
  • Endocrinology
  • Molecular Biology

Background:

  • Pancreatic beta cell dysfunction underlies type 2 diabetes (T2D).
  • Identifying novel proteins regulating beta cell stress response is critical for therapeutic development.
  • KH-type splicing regulatory protein (KSRP) impacts gene expression but its role in beta cells is unknown.

Purpose of the Study:

  • To investigate the role of KSRP in pancreatic beta cell function and survival under stress.
  • To determine if KSRP expression is altered in models of beta cell dysfunction.

Main Methods:

  • Assessed KSRP expression in pancreatic islets from diet-induced obese mice.
  • Utilized INS-1E cells exposed to stressors (palmitate, CPA) to model beta cell dysfunction.
  • Performed KSRP knockdown and overexpression experiments in beta cells.

Main Results:

  • KSRP expression was reduced in all tested beta cell dysfunction models.
  • KSRP knockdown led to increased beta cell death and impaired insulin secretion.
  • KSRP overexpression protected beta cells from death and enhanced insulin secretion.

Conclusions:

  • KSRP plays a protective role in pancreatic beta cells.
  • KSRP is a potential therapeutic target for preserving beta cell function and preventing type 2 diabetes.