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

ENGİN A. B., ENGİN A.

PROTEIN KINASE-MEDIATED DECISIONS BETWEEN LIFE AND DEATH, cilt.1275, ss.195-227, 2021 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 1275
  • Basım Tarihi: 2021
  • Doi Numarası: 10.1007/978-3-030-49844-3_8
  • Dergi Adı: PROTEIN KINASE-MEDIATED DECISIONS BETWEEN LIFE AND DEATH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.195-227
  • Anahtar Kelimeler: Type 2 diabetes ( T2D), beta-Cell dysfunction, beta-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, ENDOPLASMIC-RETICULUM STRESS, ISLET AMYLOID POLYPEPTIDE, STIMULATED INSULIN-SECRETION, N-TERMINAL KINASE, PRO-INFLAMMATORY CYTOKINES, CHRONIC OXIDATIVE STRESS, UNSATURATED FATTY-ACIDS, ARNT-SIM KINASE, INDUCED APOPTOSIS, ER STRESS
  • Gazi Üniversitesi Adresli: Evet

Özet

Type 2 diabetes (T2D) is a worldwide serious public health problem. Insulin resistance and beta-cell failure are the two major components of T2D pathology. In addition to defective endoplasmic reticulum (ER) stress signaling due to glucolipotoxicity, beta-cell dysfunction or beta-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 beta-cell fate and protein kinases pathways are discussed; hyperglycemia--induced beta-cell failure, chronic accumulation of unfolded protein in beta-cells, the effect of intracellular reactive oxygen species (ROS) signaling to insulin secretion, excessive saturated free fatty acid-induced beta-cell apoptosis, mitophagy dysfunction, proinflammatory responses and insulin resistance, and the reprogramming of beta-cell for differentiation or dedifferentiation in T2D. There is much debate about selecting proposed therapeutic strategies to maintain or enhance optimal beta-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.