Related Experiment Video

Updated: Jan 10, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

847

The effect of Dapagliflozin on diabetic nephropathy through PRMT1-SIRT1-FoxO1 pathway-mediated autophagy

Jingtong Zhao1, Chunxia Dong2, Peng Qiu3

  • 1Department of Internal Medicine, Hebei Medical University, Hebei General Hospital, Shijiazhuang, Hebei, China.

Biochemical and Biophysical Research Communications
|November 22, 2025
PubMed
Abstract

Insights

Dapagliflozin treatment improved kidney function in diabetic mice by enhancing autophagy. This occurred through the PRMT1-SIRT1-FoxO1 pathway, reducing kidney damage and disease progression.

Area of Science:

  • Nephrology
  • Endocrinology
  • Molecular Biology

Background:

  • Diabetic kidney disease (DKD) is a major complication of type 2 diabetes, characterized by progressive renal damage.
  • Autophagy plays a critical role in maintaining podocyte health and kidney function under diabetic conditions.
  • Dysregulation of the PRMT1-SIRT1-FoxO1 signaling pathway is implicated in DKD pathogenesis.

Purpose of the Study:

  • To investigate the therapeutic effect of dapagliflozin on DKD.
  • To elucidate the molecular mechanism by which dapagliflozin ameliorates DKD, focusing on the PRMT1-SIRT1-FoxO1-mediated autophagy pathway.
  • To assess dapagliflozin's role in delaying DKD progression.

Main Methods:

  • C57BL/6J mice with DKD were treated with dapagliflozin or saline for 8 weeks.
  • Biochemical parameters, renal ultrastructure (transmission electron microscopy), and protein expression (label-free quantitative proteomics, Western blot, RT-PCR, immunofluorescence) were analyzed.
  • Expression of PRMT1, SIRT1, FoxO1, and autophagy markers (LC3, p62, Beclin-1, Atg7, Atg12) was assessed.

Main Results:

  • Dapagliflozin treatment significantly reduced serum creatinine, urine albumin, BUN, and cholesterol levels.
  • Renal ultrastructure showed milder glomerular lesions in the dapagliflozin-treated group compared to the DKD group.
  • Dapagliflozin decreased PRMT1 expression while increasing SIRT1, FoxO1, and autophagy-related protein expression in renal tissue.

Conclusions:

  • Dapagliflozin effectively ameliorates renal function and pathological injury in DKD.
  • The mechanism involves restoring podocyte autophagic activity via regulation of the PRMT1-SIRT1-FoxO1 pathway.
  • Dapagliflozin shows potential in delaying the progression of diabetic kidney disease.
Keywords:
AutophagyDapagliflozinDiabetic nephropathyFoxO1PRMT1SIRT1

More Related Videos

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease08:15

Author Spotlight: Network Pharmacology and Molecular Docking to Decipher the Action of Jiawei Shengjiang San Against Diabetic Kidney Disease

Published on: May 10, 2024

901

Related Concept Videos

PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.3K
Dipeptidyl Peptidase 4 Inhibitors01:23

Dipeptidyl Peptidase 4 Inhibitors

Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
566
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
824
Oral Hypoglycemic Agents: Biguanides and Glitazones01:26

Oral Hypoglycemic Agents: Biguanides and Glitazones

Biguanides, particularly metformin (Glucophage), are insulin sensitizers that enhance glucose uptake, thereby reducing insulin resistance. Unlike sulfonylureas, metformin doesn't prompt insulin secretion, which helps to curb hypoglycemia risk. Metformin is beneficial in treating conditions like polycystic ovary syndrome due to its insulin-resistance reduction capability. The drug's primary action involves curtailing hepatic gluconeogenesis, a significant contributor to high blood...
567