Diabetes, Insulin & Glucose Scientific Publications

Latest publication 02/22/2022

Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Sign

Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by...

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    [title] => Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Sign
    [paragraph] => Painful Diabetic Neuropathy Is Associated with Compromised Microglial IGF-1 Signaling Which Can Be Rescued by Green Tea Polyphenol EGCG in Mice
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Authors
X Chen, Y Le, SQ Tang et al

 Lab
Department of Anesthesiology, The First PeopleÕs Hospital of Foshan, Foshan, Guangdong, China
Journal
Oxidative Medicine and Cellular Longevity
Abstract
Painful diabetic neuropathy (PDN) is a frequent and troublesome complication of diabetes, with little effective treatment. PDN is characterized by specific spinal microglia-mediated neuroinflammation. Insulin-like growth factor 1 (IGF-1) primarily derives from microglia in the brain and serves a vital role in averting the microglial transition into the proinflammatory M1 phenotype. Given that epigallocatechin-3-gallate (EGCG) is a potent anti-inflammatory agent that can regulate IGF-1 signaling, we speculated that EGCG administration might reduce spinal microglia-related neuroinflammation and combat the development of PDN through IGF-1/IGF1R signaling. Methods. Type 1 diabetes mellitus (T1DM) was established by a single intraperitoneal (i.p.) injection of streptozotocin (STZ) in mice. The protein expression level of IGF-1, its receptor IGF1R, interleukin 1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), and inducible nitric oxide synthase (iNOS) was determined by Western blot or immunofluorescence. Results. The spinal IGF-1 expression markedly decreased along with the presence of pain-like behaviors, the spinal genesis of neuroinflammation (increased IL-1beta, TNF-alpha, and Iba-1+ microglia), and the intensified M1 microglia polarization (increased iNOS+Iba-1+ microglia) in diabetic mice. IGF-1 could colocalize with neurons, astrocytes, and microglia, but only microglial IGF-1 was repressed in T1DM mice. Furthermore, we found that i.t. administration of mouse recombinant IGF-1 (rIGF-1) as well as i.t. or i.p. treatment with EGCG alleviated the diabetes-induced pain-like behaviors, reduced neuroinflammation (suppressed IL-1beta, TNF-alpha, and Iba-1+ microglia), prevented the M1 microglia polarization (less iNOS+Iba-1+ microglia), and restored the microglial IGF-1 expression. Conclusions. Our data highlighted the importance of maintaining spinal IGF-1 signaling in treating microglia-related neuroinflammation in PDN. This study also provides novel insights into the neuroprotective mechanisms of EGCG against neuropathic pain and neuroinflammation through IGF-1 signaling, indicating that this agent may be a promising treatment for PDN in the clinical setting.
BIOSEB Instruments Used
Electronic Von Frey 5 with embedded camera (BIO-EVF5),Electronic Von Frey 4 (BIO-EVF4)
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The EVF5 includes an embedded camera inside the stimulator handle and a new, dedicated software revolutionizing the experimental process.

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This precise and easy-to-use electronic instrument is a must-have reference for your research in analgesia, nociception, neuro-pathologies and post-operative pain.

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