Allantoin reduces glucotoxicity and lipotoxicity in a type 2 diabetes rat model by modulating the PI3K and MAPK

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Yao Zhao1, Ming Qiao2,3, Xiaomei Wang1

  • 1College of Pharmacy, Xinjiang Medical University, Urumqi, 830017, Xinjiang, China.

Heliyon
|August 15, 2024
PubMed
Abstract

Insights

Allantoin effectively treats type 2 diabetes in rats by improving insulin sensitivity and reducing inflammation. This study shows allantoin activates the PI3K pathway, offering a potential new therapy for diabetes.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Endocrinology

Background:

  • Type 2 diabetes is a metabolic disorder characterized by insulin resistance and hyperglycemia.
  • High-fat diet (HFD) and streptozotocin (STZ) induced diabetes models are widely used to study diabetes pathophysiology and test potential treatments.
  • Allantoin is a compound found in various plants, known for its healing properties, but its antidiabetic effects require further investigation.

Purpose of the Study:

  • To investigate the therapeutic potential of allantoin in a rat model of type 2 diabetes.
  • To elucidate the underlying molecular mechanisms of allantoin's antidiabetic activity.

Main Methods:

  • Type 2 diabetes was induced in male Sprague-Dawley rats using a high-fat diet and streptozotocin injection.
  • Rats were treated orally with allantoin (200, 400, and 800 mg/kg/day) for 8 weeks.
  • Metabolic parameters, oral glucose tolerance tests (OGTT), hyperinsulinemic-euglycemic clamp tests, histopathology, and Western blot analysis of signaling pathways were performed.

Main Results:

  • Allantoin significantly reduced fasting blood glucose, improved glucose tolerance, and increased insulin sensitivity.
  • Allantoin treatment decreased lipid profile levels, oxidative stress markers (MDA), and inflammatory markers (TGF-β1/p38MAPK/Caspase-3).
  • Western blot analysis revealed allantoin upregulated IRS-2/PI3K/p-Akt/GLUT expression, indicating activation of the PI3K/Akt pathway.

Conclusions:

  • Allantoin demonstrates significant antidiabetic effects in a HFD/STZ-induced rat model.
  • The therapeutic action of allantoin is mediated through the activation of the PI3K/Akt signaling pathway.
  • Allantoin reduces apoptosis and inflammation-induced insulin resistance in the liver, kidney, and pancreas.
Keywords:
AllantoinCell apoptosisInsulin resistanceOxidative stressPI3K/Akt signal pathwayType 2 diabetes mellitus

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