Related Experiment Video

Updated: Feb 13, 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

960

Enhanced insulin receptor, but not PI3K, signalling protects podocytes from ER stress

Kathryn L Garner1, Virginie M S Betin1, Vanda Pinto1

  • 1Bristol Renal, Bristol Medical School, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK.

Scientific Reports
|March 4, 2018
PubMed

Insights

Improving insulin sensitivity protects kidney podocytes from endoplasmic reticulum (ER) stress and apoptosis in diabetic nephropathy. Targeting the insulin receptor (IR) or inhibiting protein tyrosine-phosphatase 1B (PTP1B) offers protection, while PTEN knockdown sensitizes podocytes.

Area of Science:

  • Nephrology
  • Molecular Biology
  • Diabetology

Background:

  • Diabetic nephropathy involves endoplasmic reticulum (ER) stress in kidney podocytes, leading to apoptosis and proteinuria.
  • The insulin-PI3K-Akt signaling pathway is crucial in podocyte function and survival.

Purpose of the Study:

  • To investigate whether enhancing insulin sensitivity can protect kidney podocytes from ER stress.
  • To explore the roles of specific signaling molecules in ER stress response within podocytes.

Main Methods:

  • Utilized activating transcription factor 6 (ATF6)- and ER stress element (ERSE)-luciferase assays.
  • Employed a novel high-throughput imaging-based C/EBP homologous protein (CHOP) assay.
  • Examined three models of enhanced insulin sensitivity in podocytes.

Main Results:

  • Over-expressing the insulin receptor (IR) or knocking down protein tyrosine-phosphatase 1B (PTP1B) protected podocytes from ER stress induced by fatty acids or diabetic media.
  • Knocking down phosphatase and tensin homolog deleted from chromosome 10 (PTEN) sensitized podocytes to ER stress and apoptosis, despite increased Akt phosphorylation.
  • Inhibiting the MEK/ERK signaling pathway rescued PTEN knockdown podocytes from ER stress, suggesting non-PI3K-Akt pathway involvement.

Conclusions:

  • Improving insulin sensitivity, particularly at the insulin receptor level, can protect podocytes from ER stress.
  • Podocyte protection from ER stress involves complex signaling pathways beyond just PI3K-Akt.
  • Targeting specific regulators of insulin signaling may offer therapeutic strategies for diabetic nephropathy.

More Related Videos

Author Spotlight: Generation of Patient-Derived Podocytes from Skin Biopsies08:52

Author Spotlight: Generation of Patient-Derived Podocytes from Skin Biopsies

Published on: May 26, 2023

3.1K
Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain08:32

Studying the Hypothalamic Insulin Signal to Peripheral Glucose Intolerance with a Continuous Drug Infusion System into the Mouse Brain

Published on: January 4, 2018

10.9K

Related Concept Videos

Insulin: The Receptor and Signaling Pathways01:28

Insulin: The Receptor and Signaling Pathways

Insulin action is mediated through a receptor tyrosine kinase, akin to the IGF-1 receptor. The number of receptors per cell varies significantly, from 40 on erythrocytes to 300,000 on adipocytes and hepatocytes. The insulin receptor consists of linked α/β subunit dimers, forming a heterotetramer glycoprotein with two extracellular α subunits and two β subunits spanning the membrane. The α subunits inhibit the inherent tyrosine kinase activity of the β subunits, but...
3.5K
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...
5.7K
Signal Sequences and Sorting Receptors01:41

Signal Sequences and Sorting Receptors

Signal sequences are short amino acid sequences that guide newly synthesized proteins to their proper location within the cell. Classical signal sequences are fifteen to sixty amino acids long and present at the N-terminus of a polypeptide chain. Each signal sequence has a conserved segment of basic residues towards their N terminus, a hydrophobic core, and a C-terminus rich in polar residues. The C-terminus also contains a signal cleavage site and features a -3 -1 sequence motif. The -3-1...
15.5K
Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists01:30

Cognitive Enhancers: Cholinesterase Inhibitors and NMDA Receptor Antagonists

Cognitive enhancers, also known as "smart drugs," are substances used to enhance memory, mental alertness, and concentration. These can be natural or synthetic and improve cognition in conditions like Alzheimer's disease (AD) and other neurodegenerative diseases. Some common examples include caffeine, amphetamines, methylphenidate, modafinil, arecoline, donepezil, vortioxetine, and piracetam. These enhancers work on the principle of synaptic plasticity and altered circuit function.
663
Yeast Signaling01:28

Yeast Signaling

Yeasts are single-celled organisms, but unlike bacteria, they are eukaryotes (cells with a nucleus). Cell signaling in yeast is similar to signaling in other eukaryotic cells. A ligand, such as a protein or a small molecule released from a yeast cell, attaches to a receptor on the cell surface. The binding stimulates second-messenger kinases to activate or inactivate transcription factors that further regulate gene expression. Many of the yeast intracellular signaling cascades have similar...
17.3K
Endocrine Signaling01:45

Endocrine Signaling

Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
68.2K