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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.
This article was published in the following journal.
Name: Cell reports
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...
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. ...
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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...
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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 188.8.131.52.
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.
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...
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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...