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Dipeptidyl Peptidase (DPP)-4 Inhibitors and Pituitary Adenylate Cyclase-Activating Polypeptide, a DPP-4 Substrate, Extend Neurite Outgrowth of Mouse Dorsal Root Ganglia Neurons: A Promising Approach in Diabetic Polyneuropathy Treatment.
Yamaguchi, Masahiro; Noda-Asano, Saeko; Inoue, Rieko; Himeno, Tatsuhito; Motegi, Mikio; Hayami, Tomohide; Nakai-Shimoda, Hiromi; Kono, Ayumi; Sasajima, Sachiko; Miura-Yura, Emiri; Morishita, Yoshiaki; Kondo, Masaki; Tsunekawa, Shin; Kato, Yoshiro; Kato, Koichi; Naruse, Keiko; Nakamura, Jiro; Kamiya, Hideki.
Afiliación
  • Yamaguchi M; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Noda-Asano S; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Inoue R; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Himeno T; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Motegi M; Department of Innovative Diabetes Therapy, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Hayami T; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Nakai-Shimoda H; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Kono A; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Sasajima S; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Miura-Yura E; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Morishita Y; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Kondo M; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Tsunekawa S; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Kato Y; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Kato K; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
  • Naruse K; Department of Medicine, Aichi Gakuin University School of Pharmacy, Nagoya 464-8650, Japan.
  • Nakamura J; Department of Internal Medicine, Aichi Gakuin University School of Dentistry, Nagoya 464-0821, Japan.
  • Kamiya H; Division of Diabetes, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1185, Japan.
Int J Mol Sci ; 25(16)2024 Aug 15.
Article en En | MEDLINE | ID: mdl-39201570
ABSTRACT
Individuals suffering from diabetic polyneuropathy (DPN) experience debilitating symptoms such as pain, paranesthesia, and sensory disturbances, prompting a quest for effective treatments. Dipeptidyl-peptidase (DPP)-4 inhibitors, recognized for their potential in ameliorating DPN, have sparked interest, yet the precise mechanism underlying their neurotrophic impact on the peripheral nerve system (PNS) remains elusive. Our study delves into the neurotrophic effects of DPP-4 inhibitors, including Diprotin A, linagliptin, and sitagliptin, alongside pituitary adenylate cyclase-activating polypeptide (PACAP), Neuropeptide Y (NPY), and Stromal cell-derived factor (SDF)-1a-known DPP-4 substrates with neurotrophic properties. Utilizing primary culture dorsal root ganglia (DRG) neurons, we meticulously evaluated neurite outgrowth in response to these agents. Remarkably, all DPP-4 inhibitors and PACAP demonstrated a significant elongation of neurite length in DRG neurons (PACAP 0.1 µM 2221 ± 466 µm, control 1379 ± 420, p < 0.0001), underscoring their potential in nerve regeneration. Conversely, NPY and SDF-1a failed to induce neurite elongation, accentuating the unique neurotrophic properties of DPP-4 inhibition and PACAP. Our findings suggest that the upregulation of PACAP, facilitated by DPP-4 inhibition, plays a pivotal role in promoting neurite elongation within the PNS, presenting a promising avenue for the development of novel DPN therapies with enhanced neurodegenerative capabilities.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropatías Diabéticas / Polipéptido Hipofisario Activador de la Adenilato-Ciclasa / Inhibidores de la Dipeptidil-Peptidasa IV / Proyección Neuronal / Ganglios Espinales Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza
Texto completo
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Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neuropatías Diabéticas / Polipéptido Hipofisario Activador de la Adenilato-Ciclasa / Inhibidores de la Dipeptidil-Peptidasa IV / Proyección Neuronal / Ganglios Espinales Límite: Animals Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Suiza