Related Experiment Video

Updated: Mar 18, 2026

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory
10:03

A Zebrafish Model of Diabetes Mellitus and Metabolic Memory

Published on: February 28, 2013

26.7K

Targeting Select Cellular Stress Pathways to Prevent Hyperglycemia-Related Complications: Shifting the Paradigm

Arshag D Mooradian1

  • 1Department of Medicine, University of Florida College of Medicine, 653-1 West Eighth Street, Jacksonville, FL, 32209, USA. arshag.mooradian@jax.ufl.edu.

Drugs
|July 2, 2016
PubMed

Insights

New diabetes therapies should target multiple cellular stresses, not just oxidative stress. Addressing oxidative, ER, mitochondrial, and inflammatory stresses simultaneously offers a more effective approach to preventing diabetic complications.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Diabetology

Background:

  • Despite advances, diabetes complications pose significant risks.
  • Glucotoxicity involves polyol, protein kinase C (PKC), glycosylation, and oxidative stress pathways.
  • Emerging research highlights crosstalk between oxidative stress and ER, inflammatory, and mitochondrial stresses.

Purpose of the Study:

  • To review the multifaceted pathogenesis of diabetic complications.
  • To evaluate the limitations of targeting individual stress pathways.
  • To propose a novel therapeutic strategy for diabetic complications.

Main Methods:

  • Literature review of biochemical pathways contributing to glucotoxicity.
  • Analysis of the role of cellular stress crosstalk in diabetes.
  • Evaluation of antioxidant therapy outcomes in diabetic research.

Main Results:

  • Oxidative stress is a central but not sole contributor to glucotoxicity.
  • Targeting only oxidative stress with antioxidants has yielded unfavorable clinical outcomes.
  • Antioxidants may exacerbate endoplasmic reticulum (ER) stress in certain contexts.

Conclusions:

  • Selective targeting of individual cellular stresses is insufficient for preventing diabetic complications.
  • Future therapeutic agents should aim to globally ameliorate cellular stress.
  • Simultaneous targeting of oxidative, ER, mitochondrial, and inflammatory stresses is a promising strategy.

More Related Videos

Author Spotlight: Investigating the Blood Glucose Homeostasis in Murine Brain Using a Cost-Effective Hyperglycemic And Hypoglycemic Clamp Technique07:35

Author Spotlight: Investigating the Blood Glucose Homeostasis in Murine Brain Using a Cost-Effective Hyperglycemic And Hypoglycemic Clamp Technique

Published on: January 26, 2024

2.3K
A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals07:39

A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals

Published on: June 25, 2018

7.8K

Related Concept Videos

Hypoglycemia and Glucagon01:15

Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the...
1.2K
Psychoneuroimmunology: Diabetes and Cancer01:19

Psychoneuroimmunology: Diabetes and Cancer

Chronic stress has been linked to both the onset and progression of serious health conditions, including Type 2 diabetes and cancer. Type 2 diabetes, a widespread chronic illness, is closely associated with obesity and insulin resistance, both of which often worsen under stress. Studies indicate that men experiencing high levels of chronic stress face a 45% higher risk of developing diabetes compared to those with minimal stress. Stress triggers physiological responses that elevate blood...
600
Hormones Regulating Blood Glucose01:16

Hormones Regulating Blood Glucose

Insulin is released by beta cells of the pancreas when blood glucose levels are high. It facilitates glucose absorption and utilization in insulin-dependent cells with insulin receptors on their plasma membranes. Insulin promotes glucose uptake by increasing the number of glucose transport proteins in the cell membrane, allowing glucose to enter the cell. As a result, glucose utilization and ATP production are enhanced.
In addition to accelerating glucose uptake and utilization, insulin has...
8.2K
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...
871
Diabetes: Management and Pharmacotherapy01:15

Diabetes: Management and Pharmacotherapy

The therapy for diabetes aims to alleviate hyperglycemia-related symptoms, prevent acute metabolic decompensation, and reduce chronic end-organ complications. Glycemic control is evaluated through short-term (self-monitoring, continuous glucose monitoring) and long-term (A1c, fructosamine) metrics, enabling near real-time tracking of blood glucose levels and reflecting glycemic control over specific time frames.
Insulin remains the cornerstone of treatment for most patients with type 1 and many...
1.3K
Diabetes: Symptoms, Diagnosis, and Complications01:15

Diabetes: Symptoms, Diagnosis, and Complications

For most patients, experiencing several weeks of polyuria, polydipsia, fatigue, and significant weight loss may indicate the presence of diabetes. Furthermore, adults displaying the phenotypic appearance of type 2 diabetes (particularly those who are obese and not initially insulin-requiring), may have islet cell autoantibodies, suggesting autoimmune-mediated β cell destruction and a diagnosis of latent autoimmune diabetes of adults (LADA). The categorization of glucose homeostasis is...
2.7K