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Targeting AMPK/PI3K/AKT/mTOR pathway ameliorates kidney injury induced by type 2 diabetes

Nahla Hussien1, Yasmine Gamal Sabry1, Ansam Aly Seif1

  • 1Physiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Journal of Diabetes and Metabolic Disorders
|February 27, 2026
PubMed

Insights

Nigella sativa (NS) ameliorates kidney injury in type 2 diabetes (T2D) by modulating the AMPK/PI3K/AKT/mTOR pathway. This natural compound demonstrates significant antidiabetic, antihyperlipidemic, and renoprotective effects in T2D models.

Area of Science:

  • Biochemistry
  • Pharmacology
  • Nephrology

Background:

  • Type 2 diabetes (T2D) is a major cause of chronic kidney disease.
  • The AMPK/PI3K/AKT/mTOR pathway plays a critical role in T2D-related kidney injury.
  • Nigella sativa (NS) is a traditional herb with potential therapeutic properties.

Purpose of the Study:

  • To investigate the renoprotective effects of Nigella sativa (NS) in a rat model of type 2 diabetes (T2D).
  • To elucidate the role of the AMPK/PI3K/AKT/mTOR signaling pathway in T2D-induced kidney damage and the impact of NS treatment.

Main Methods:

  • Induction of T2D in rats and treatment with Nigella sativa (NS).
  • Assessment of renal function, lipid profile, glucose metabolism, and insulin resistance.
  • Analysis of gene expression for AMPK, PI3K, AKT, mTOR, HIF-1α, and VEGF via RT-qPCR.
  • Histopathological examination of kidney tissues using H&E staining.

Main Results:

  • T2D rats exhibited hyperglycemia, dyslipidemia, impaired renal function, and microalbuminuria.
  • T2D led to altered expression of AMPK/PI3K/AKT/mTOR pathway components and increased HIF-1α and VEGF.
  • NS treatment significantly improved biochemical parameters and reversed histopathological damage in T2D rats.
  • NS normalized the expression of key signaling molecules, indicating pathway modulation.

Conclusions:

  • Nigella sativa (NS) exerts significant renoprotective, antidiabetic, and antihyperlipidemic effects in type 2 diabetes (T2D).
  • The beneficial effects of NS are associated with the modulation of the AMPK/PI3K/AKT/mTOR signaling pathway.
  • NS holds promise as a therapeutic agent for managing diabetic nephropathy.

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