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Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes

Chapter
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1275)

Abstract

Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and β-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, β-cell dysfunction or β-cell death initiates the deleterious vicious cycle observed in T2D. Although the primary cause is still unknown, overnutrition that contributes to the induction of the state of low-grade inflammation, and the activation of various protein kinases-related metabolic pathways are main factors leading to T2D. In this chapter following subjects, which have critical checkpoints regarding β-cell fate and protein kinases pathways are discussed; hyperglycemia-induced β-cell failure, chronic accumulation of unfolded protein in β-cells, the effect of intracellular reactive oxygen species (ROS) signaling to insulin secretion, excessive saturated free fatty acid-induced β-cell apoptosis, mitophagy dysfunction, proinflammatory responses and insulin resistance, and the reprogramming of β-cell for differentiation or dedifferentiation in T2D. There is much debate about selecting proposed therapeutic strategies to maintain or enhance optimal β-cell viability for adequate insulin secretion in T2D. However, in order to achieve an effective solution in the treatment of T2D, more intensive clinical trials are required on newer therapeutic options based on protein kinases signaling pathways.

Keywords

Type 2 diabetes (T2D) β-Cell dysfunction β-Cell death Saturated free fatty acids (SFFA) Glucose-stimulated insulin secretion (GSIS) Reactive oxygen species (ROS) Reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase Human islet amyloid polypeptide (hIAPP) Fas receptors (FasR) ER (endoplasmic reticulum) stress 
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Authors and Affiliations

  1. 1.Department of Toxicology, Faculty of PharmacyGazi UniversityAnkaraTurkey
  2. 2.Department of General Surgery, Faculty of MedicineGazi UniversityAnkaraTurkey

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