Related Experiment Video
Updated: Dec 13, 2025
08:01
Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
6.4K
Increased Glucose Availability Attenuates Myocardial Ketone Body Utilization.
Manoja K Brahma1, Chae-Myeong Ha1, Mark E Pepin1,2
1Departments of Pathology Division of Molecular and Cellular Pathology University of Alabama at Birmingham AL USA.
Journal of the American Heart Association
|August 5, 2020
Summary
Diabetic hearts show reduced ketone utilization due to high glucose. This study reveals that increased glucose suppresses cardiac ketolytic capacity, impacting heart function in diabetes.
Area of Science:
- Cardiology
- Metabolic Research
- Biochemistry
Background:
- Cardiac dysfunction in diabetes is linked to altered myocardial substrate utilization.
- Failing hearts shift from fatty acid/glucose to ketone oxidation, but this mechanism is unclear in diabetes.
- The interplay between glucose and ketone metabolism in diabetic hearts requires further investigation.
Purpose of the Study:
- To test if changes in myocardial glucose utilization influence ketone body catabolism in diabetes.
- To elucidate the mechanisms mediating substrate shifts in the diabetic heart.
Main Methods:
- Utilized murine models: type 1 diabetes, high-fat diet-induced glucose intolerance, and transgenic models for glucose transporter 4 and O-GlcNAcase.
- Examined cardiac tissue for gene/protein expression and metabolic activity.
- Performed transcriptomic analysis on human patient samples (type 2 diabetes with heart failure).
Main Results:
- Elevated blood glucose reduced cardiac expression of key ketone utilization enzymes (β-hydroxybutyrate-dehydrogenase, succinyl-CoA:3-oxoacid CoA transferase).
- Increased glucose delivery impaired cardiac ketone oxidation and enzyme activity.
- Elevated O-GlcNAcylation suppressed β-hydroxybutyrate dehydrogenase expression.
- Suppression of ketone utilization genes (BDH1, OXCT1) was confirmed in human diabetic heart failure patients.
Conclusions:
- Increased myocardial glucose suppresses cardiac ketolytic capacity via multiple mechanisms.
- Identified a crosstalk between glucose and ketone body metabolism in the diabetic myocardium.
- Provides evidence for impaired ketone utilization contributing to diabetic cardiomyopathy.
Keywords:
O‐GlcNAcylationcardiomyopathydiabetes mellitusdiabetic cardiomyopathyglucoseketone metabolismmitochondriaMore Related Videos
Related Concept Videos
01:02Glucose Homeostasis: Regulation of Blood Glucose
3.5K
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...
During fasting, when blood glucose levels are low, the pancreas secretes glucagon. it...
3.5K
01:24Metabolic States of the Body: Fasting and Starvation
2.4K
During the initial hours of fasting, the body uses up its glycogen stores as an energy source. Once these glycogen reserves are depleted, the body begins breaking down stored triglycerides and structural proteins. During this stage, glycerol becomes a key substrate for gluconeogenesis, while free fatty acids undergo beta-oxidation to provide energy for tissues, such as skeletal muscle. In the fasting state, the body spares protein breakdown as much as possible to conserve muscle and structural...
2.4K
01:18Metabolic States of the Body: The Postabsorptive State
1.1K
The postabsorptive state usually starts about four hours after a meal and lasts until the next meal is eaten. During this time, the digestive system stops absorbing nutrients, and the body uses stored energy reserves to maintain stable blood glucose levels.
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...
Initially, glycogen stored in the liver is broken down to release glucose into the bloodstream, while glycogen in the muscles is broken down to supply glucose for energy directly within the muscle cells. As glycogen stores diminish,...
1.1K
01:16Hormones Regulating Blood Glucose
6.0K
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...
In addition to accelerating glucose uptake and utilization, insulin has...
6.0K
01:19Overview of Carbohydrate Metabolism
2.8K
Carbohydrate metabolism is a fundamental biochemical process that ensures a constant supply of energy to living cells. The most important carbohydrate is glucose, which can be broken down via glycolysis to enter into the Krebs cycle and eventually lead to the production of ATP through oxidative phosphorylation.
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
Glucose transport into cells is facilitated by a family of transport proteins called GLUT (Glucose Transporters). GLUT4 is the primary glucose transporter for insulin-stimulated glucose...
2.8K
01:15Hypoglycemia and Glucagon
674
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...
674