title: Neuroprotective effect of the glucagon-like peptide-1 receptor agonist, synthetic exendin-4, in streptozotocin-induced diabetic rats.
abstract: OBJECTIVE
  Glucagon-like peptide-1 (GLP-1) receptors are widely expressed in neural tissues and diminish neuronal degeneration or induce neuronal differentiation. The aim of this study was to investigate the effect of the GLP-1 pathway on peripheral nerves in streptozotocin-induced diabetic rats.
  
  
  METHODS
  Diabetic and nondiabetic rats were treated with the GLP-1 receptor agonist, synthetic exendin-4 (i.p., 1 nmol·kg(-1)·day(-1)) or placebo for 24 weeks, and current perception threshold values, cAMP levels and nerve fibre size in the sciatic nerve were measured. We also investigated GLP-1 receptor expression, quantitative changes in PGP9.5-positive intraepidermal nerve fibres and cleaved caspase 3-stained Schwann cells by immunohistochemistry.
  
  
  RESULTS
  GLP-1 receptor expression was detected in the sciatic nerve and skin. After exendin-4 treatment, the increase seen in current perception threshold values at 2000 and 250 Hz in diabetic rats was reduced. Also, the decrease in myelinated fibre size or axon/fibre area ratio in the sciatic nerve and the loss of intraepidermal nerve fibre in the skin of diabetic rats were ameliorated. These responses were closely associated with the attenuation of Schwann cell apoptosis and improvement in the cAMP level in exendin-4-treated diabetic rats, compared with placebo-treated animals.
  
  
  CONCLUSIONS
  Synthetic exendin-4 may prevent peripheral nerve degeneration induced by diabetes in an animal model, supporting the hypothesis that GLP-1 may be useful in peripheral neuropathy. The neuroprotection is probably attributable to GLP-1 receptor activation, antiapoptotic effects and restoration of cAMP content.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: Wei Jing
authors.initials: WJ
authors.lastname: Liu
authors.forename: Heung Yong
authors.initials: HY
authors.lastname: Jin
authors.forename: Kyung Ae
authors.initials: KA
authors.lastname: Lee
authors.forename: Shu Hua
authors.initials: SH
authors.lastname: Xie
authors.forename: Hong Sun
authors.initials: HS
authors.lastname: Baek
authors.forename: Tae Sun
authors.initials: TS
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D005951:Glucose Tolerance Test; D006442:Glycated Hemoglobin / Q000032:analysis; D007328:Insulin / Q000097:blood; D008297:Male; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D010455:Peptides / Q000008:administration & dosage / Q000627:therapeutic use*; D017933:Peripheral Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000819:agonists*; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D012867:Skin / Q000378:metabolism; D013311:Streptozocin / Q000494:pharmacology; D014688:Venoms / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D001786:Blood Glucose; D000242:Cyclic AMP; D000077270:Exenatide; D000067757:Glucagon-Like Peptide-1 Receptor; D006442:Glycated Hemoglobin; D007328:Insulin; D018696:Neuroprotective Agents; D010455:Peptides; D018027:Receptors, Glucagon; D013311:Streptozocin; D014688:Venoms; C000593835:Glp1r protein, rat