CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets.

08:00 EDT 12th June 2018 | BioPortfolio

Summary of "CPT1a-Dependent Long-Chain Fatty Acid Oxidation Contributes to Maintaining Glucagon Secretion from Pancreatic Islets."

Glucagon, the principal hyperglycemic hormone, is secreted from pancreatic islet α cells as part of the counter-regulatory response to hypoglycemia. Hence, secretory output from α cells is under high demand in conditions of low glucose supply. Many tissues oxidize fat as an alternate energy substrate. Here, we show that glucagon secretion in low glucose conditions is maintained by fatty acid metabolism in both mouse and human islets, and that inhibiting this metabolic pathway profoundly decreases glucagon output by depolarizing α cell membrane potential and decreasing action potential amplitude. We demonstrate, by using experimental and computational approaches, that this is not mediated by the K channel, but instead due to reduced operation of the Na-K pump. These data suggest that counter-regulatory secretion of glucagon is driven by fatty acid metabolism, and that the Na-K pump is an important ATP-dependent regulator of α cell function.


Journal Details

This article was published in the following journal.

Name: Cell reports
ISSN: 2211-1247
Pages: 3300-3311


DeepDyve research library

PubMed Articles [24719 Associated PubMed Articles listed on BioPortfolio]

Development of a Genetic and Clinical Data-Based (GC) Risk Score for Predicting Survival of Hepatocellular Carcinoma Patients After Tumor Resection.

Carnitine palmitoyltransferase 1A (CPT1A) is a rate-limiting enzyme in the transport of long-chain fatty acids for β-oxidation. Increasing evidence has indicated that CPT1A plays an important role in...

CPT1A-mediated fatty acid oxidation promotes colorectal cancer cell metastasis by inhibiting anoikis.

Anoikis is a critical obstacle to cancer metastasis. Colorectal cancer (CRC) exhibits a high rate of metastasis, leading to death, and the mechanisms involved in anoikis resistance are still unclear. ...

Fatty Acid Oxidation in Macrophages and T Cells: Time for Reassessment?

Previous immunometabolism research using the CPT1 inhibitor etomoxir suggests that long-chain fatty acid oxidation (LC-FAO) supports IL-4-driven alternative macrophage activation (M(IL-4)) and regulat...

PPARβ/δ-agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes.

Astrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective f...

β-Oxidation in ghrelin-producing cells is important for ghrelin acyl-modification.

Ghrelin is a unique fatty acid-modified peptide hormone produced in the stomach and has important roles in energy homeostasis and gastrointestinal motility. However, the medium-chain fatty acid source...

Clinical Trials [7882 Associated Clinical Trials listed on BioPortfolio]

Study of Triheptanoin for Treatment of Long-Chain Fatty Acid Oxidation Disorder

Humans eat long-chain fat in their diet and use it for energy during exercise and during periods of fasting. Patients with long-chain fatty acid oxidation disorders cannot use dietary fat ...

Fatty Acid Oxidation Defects and Insulin Sensitivity

The purpose of this study is to learn more about what causes insulin resistance. It has been suggested that proper breakdown of fat into energy (oxidation) in the body is important to all...

Clinical Outcome of Triheptanoin Treatment in Patients With Long-chain Fatty Acid Oxidation Disorders (LC-FAOD) Treated Under Expanded Access Program

The primary objective of the study is to evaluate the clinical outcomes for the trigger event of patients who receive triheptanoin in the emergency Investigational New Drug (eIND) program.

Nutritional Therapy of the Deficits of Oxidation Mitochondrial of the Fatty Acids

Usual dietary therapies of mitochondrial fatty acid oxidation disorders (FAO) are based on 3 strategies: - limitation of lipid intake in the diet; - supplementation of the di...

Experiment 2: Understanding Liver Fat Metabolism

There is a largely unsubstantiated thought in the literature that dietary unsaturated enter oxidation pathways preferentially compared to saturated fatty acids. This study is undertaking a...

Medical and Biotech [MESH] Definitions

A long-chain fatty acid ester of carnitine which facilitates the transfer of long-chain fatty acids from cytoplasm into mitochondria during the oxidation of fatty acids.

A perilipin that functions in LIPOGENESIS; LIPOLYSIS; and fatty acid oxidation in BROWN ADIPOSE TISSUE; heart, liver, and skeletal muscle. It recruits MITOCHONDRIA to the surface of LIPID DROPLETS where it functions in both the storage of fatty acids as TRIGLYCERIDES, and their release for mitochondrial fatty acid oxidation in response to metabolic needs.

A flavoprotein oxidoreductase that has specificity for long-chain fatty acids. It forms a complex with ELECTRON-TRANSFERRING FLAVOPROTEINS and conveys reducing equivalents to UBIQUINONE.

Enzymes that reversibly catalyze the oxidation of a 3-hydroxyacyl CoA to 3-ketoacyl CoA in the presence of NAD. They are key enzymes in the oxidation of fatty acids and in mitochondrial fatty acid synthesis. EC

Enzyme that catalyzes the final step of fatty acid oxidation in which ACETYL COA is released and the CoA ester of a fatty acid two carbons shorter is formed.

Quick Search


DeepDyve research library

Relevant Topics

Pancreatic Cancer
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...

Diabetes Diabetes Endocrine Disorders Obesity Oxycontin Renal Disease Thyroid Disorders Endocrinology is the study of the endocrine glands and the hormones that they secrete (Oxford Medical Dictionary). There are several g...

Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake.  Diagnosis is based on clinical presentation...

Searches Linking to this Article