Related Experiment Video

Updated: Jan 27, 2026

Live Imaging of Apoptotic Cell Clearance during Drosophila Embryogenesis

Live Imaging of Apoptotic Cell Clearance during Drosophila Embryogenesis

Published on: August 18, 2013

Prompt apoptotic response to high glucose in SGLT-expressing renal cells

Linnéa M Nilsson¹, Liang Zhang², Alexander Bondar³

¹Science for Life Laboratory, Department of Applied Physics, Royal Institute of Technology, Solna, Sweden.

American Journal of Physiology. Renal Physiology

|March 14, 2019

Abstract:

It is generally believed that cells that are unable to downregulate glucose transport are particularly vulnerable to hyperglycemia. Yet, little is known about the relation between expression of glucose transporters and acute toxic effects of high glucose exposure. In the present ex vivo study of rat renal cells, we compared the apoptotic response to a moderate increase in glucose concentration. We studied cell types that commonly are targeted in diabetic kidney disease (DKD): proximal tubule cells, which express Na⁺-dependent glucose transporter (SGLT)2, mesangial cells, which express SGLT1, and podocytes, which lack SGLT and take up glucose via insulin-dependent glucose transporter 4. Proximal tubule cells and mesangial cells responded within 4-8 h of exposure to 15 mM glucose with translocation of the apoptotic protein Bax to mitochondria and an increased apoptotic index. SGLT downregulation and exposure to SGLT inhibitors abolished the apoptotic response. The onset of overt DKD generally coincides with the onset of albuminuria. Albumin had an additive effect on the apoptotic response. Ouabain, which interferes with the apoptotic onset, rescued from the apoptotic response. Insulin-supplemented podocytes remained resistant to 15 and 30 mM glucose for at least 24 h. Our study points to a previously unappreciated role of SGLT-dependent glucose uptake as a risk factor for diabetic complications and highlights the importance of therapeutic approaches that specifically target the different cell types in DKD.

Insights

High glucose levels trigger cell death in kidney cells expressing sodium-glucose cotransporter (SGLT) proteins, a key factor in diabetic kidney disease. Targeting SGLT offers a new therapeutic avenue for diabetic complications.

Area of Science:

Nephrology
Cell Biology
Metabolic Diseases

Background:

Hyperglycemia is a hallmark of diabetes, leading to diabetic kidney disease (DKD).
The role of specific glucose transporters in the acute cellular response to high glucose is not fully understood.
Kidney cell types targeted in DKD, including proximal tubule cells, mesangial cells, and podocytes, exhibit differential glucose transporter expression.

Purpose of the Study:

To investigate the relationship between glucose transporter expression and the acute apoptotic response to hyperglycemia in different rat renal cell types.
To determine the role of sodium-glucose cotransporter (SGLT)-dependent glucose uptake in high glucose-induced apoptosis.
To explore potential therapeutic strategies targeting SGLT in the context of DKD.

Main Methods:

Ex vivo study using rat renal cells (proximal tubule cells, mesangial cells, podocytes).
Exposure to moderate increases in glucose concentration (15 mM) and albumin.
Assessment of apoptotic markers (Bax translocation, apoptotic index), SGLT activity, and response to SGLT inhibitors and ouabain.

Main Results:

Proximal tubule cells (SGLT2) and mesangial cells (SGLT1) showed increased apoptosis within 4-8 hours of high glucose exposure.
Downregulation of SGLT or treatment with SGLT inhibitors abolished the apoptotic response in these cells.
Albumin exacerbated the apoptotic response, while ouabain provided protection.
Podocytes, lacking SGLT and utilizing glucose transporter 4 (GLUT4), remained resistant to high glucose.

Conclusions:

SGLT-dependent glucose uptake is a significant risk factor for acute cellular injury in DKD.
Targeting SGLT transporters may offer a novel therapeutic approach for preventing or treating diabetic kidney complications.
Differential glucose transporter expression influences cell-type-specific vulnerability to hyperglycemia in the kidney.

Read full analysis

Keywords:

apoptosis hyperglycemia podocytes proximal tubular cells sodium-dependent glucose transporter

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

A Simple Flow Cytometric Method to Measure Glucose Uptake and Glucose Transporter Expression for Monocyte Subpopulations in Whole Blood

A Simple Flow Cytometric Method to Measure Glucose Uptake and Glucose Transporter Expression for Monocyte Subpopulations in Whole Blood

Published on: August 12, 2016

Related Concept Videos

Phagocytosis of Apoptotic Cells

Phagocytosis of Apoptotic Cells

Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...

Cell Specific Gene Expression

Cell Specific Gene Expression

Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...

The Extrinsic Apoptotic Pathway

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...

The Intrinsic Apoptotic Pathway

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

Glucose Homeostasis: Regulation of Blood Glucose

Glucose Homeostasis: Regulation of Blood Glucose

Carbohydrates consumed through foods are converted into glucose, a crucial energy source for the body. In the prandial state, high blood glucose levels stimulate the secretion of insulin from the pancreas. Insulin inhibits hepatic glucose production and stimulates glucose uptake and metabolism by muscle and adipose tissue. The excess glucose is converted into glycogen and stored in the liver and muscles.
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...

Glucose Transporters

Glucose Transporters

Glucose transporters facilitate the transport of glucose across the cell membrane. In addition to glucose, some glucose transporters can also aid the movement of other hexoses such as fructose, mannose, and galactose.
Facilitated diffusion-glucose transporters (GLUTs) are encoded by the solute-linked carrier (SLC) family 2, subfamily A gene family, or SLC2A. The 14 GLUT protein members are distributed into three classes:

Articles linked to this work by shared authors, journal, and citation graph.

Integrating GlycoSHIELD Modeling and DNA-PAINT SMLM to Map the Glycosylation-Dependent Distribution of the Na,K-ATPase.

The Journal of membrane biology·2026

FN-silk membrane enables alveologenesis processes and self-organization of the H441 epithelial cell line into native-like alveolar morphology.

Scientific reports·2026

"I was planning my funeral": A qualitative study of junior physicians' experiences of self-sacrifice during the COVID-19 pandemic through the lens of physicians' social contract.

Social science & medicine (1982)·2026

The renal response to FGF23 shifts from phosphaturia toward inflammation in kidney disease.

Journal of cell communication and signaling·2026

Protection, preparation or processing support for medical students' emotional challenges in work-based learning-a grounded theory.

Advances in health sciences education : theory and practice·2026

Dual-Color Expansion Microscopy of Membrane Proteins Using Bioorthogonal Labeling.

Nano letters·2026

See all related articles