Therapeutic efficacy of arginine-rich exenatide on diabetic neuropathy in rats

Eur J Pharmacol. 2020 Jan 5;866:172835. doi: 10.1016/j.ejphar.2019.172835. Epub 2019 Nov 30.


Diabetes mellitus is characterized by metabolic dysregulation associated with a number of health complications. More than 50% of patients with diabetes mellitus suffer from diabetic polyneuropathy, which involves the presence of peripheral nerve dysfunction symptoms. The aim of this study was to evaluate the potential of a new synthetic arginine-rich exendin-4 (Peptide D) in the treatment of complications caused by diabetes, including peripheral neuropathy, in rats. Diabetes was induced by administering streptozotocin (STZ). Three groups of diabetic rats were treated with Peptide D (0.1, 1, and 10 μg/kg). One group of diabetic rats was treated with Byetta® (1 μg/kg) for 80 days. Neuropathic pain development was assessed by tactile allodynia. STZ-treated rats showed an increased level of tactile allodynia unlike naïve animals. A histological study revealed that the diameter of the sciatic nerve fibers in STZ-treated rats was smaller than that of the naïve animals. An IHC study demonstrated decreased expression of myelin basic protein (MBP) in the sciatic nerve of diabetic rats compared to that in the naïve animals. Peptide D reduced the severity of tactile allodynia. This effect was more pronounced in the Peptide D treated groups than in the group treated with Byetta®. Peptide D and Byetta® treatment resulted in increased MBP expression in the sciatic nerve and increased diameter of myelinated nerve fibers. These findings suggest that poly-arginine peptides are promising agents for the treatment of peripheral polyneuropathies.

Keywords: Diabetes mellitus; Exenatide; Peripheral neuropathy; Poly-arginine; Rat.

MeSH terms

  • Animals
  • Arginine / chemistry*
  • Blood Glucose / metabolism
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / drug therapy*
  • Diabetic Neuropathies / pathology
  • Diabetic Neuropathies / physiopathology
  • Dose-Response Relationship, Drug
  • Exenatide / chemistry*
  • Exenatide / pharmacology*
  • Exenatide / therapeutic use
  • Gene Expression Regulation / drug effects
  • Glycated Hemoglobin / metabolism
  • Hyperalgesia / complications
  • Insulin / metabolism
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / pathology
  • Locomotion / drug effects
  • Male
  • Organ Size / drug effects
  • Rats
  • Rats, Wistar
  • Sciatic Nerve / drug effects
  • Sciatic Nerve / pathology


  • Blood Glucose
  • Glycated Hemoglobin A
  • Insulin
  • Arginine
  • Exenatide