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Plasma amino acids and their transporters constitute an important part of the feedback loop between the liver and pancreatic α-cell function, and glucagon regulates hepatic amino acid turnover. Disruption of hepatic glucagon receptor action activates the loop and results in high plasma amino acids and hypersecretion of glucagon associated with α-cell hyperplasia. In the present study, we report a technique to rescue implanted human pancreatic islets from the mouse kidney capsule. Using this model, we have demonstrated that expression of the amino acid transporter SLC38A4 increases in α-cells after administration of a glucagon receptor blocking antibody. The increase in SLC38A4 expression and associated α-cell proliferation was dependent on mechanistic target of rapamycin pathway. We confirmed increased α-cell proliferation and expression of SLC38A4 in pancreas sections from patients with glucagon cell hyperplasia and neoplasia (GCHN) with loss-of-function mutations in the glucagon receptor. Collectively, using a technique to rescue implanted human islets from the kidney capsule in mice and pancreas sections from patients with GCHN, we found that expression of SLC38A4 was increased under conditions of disrupted glucagon receptor signaling. These data provide support for the existence of a liver-human α-cell endocrine feedback loop.
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Amino acid transporters are necessary for tumor growth, metastasis, and survival of various neoplasms; however, the clinicopathological significance of L-type amino acid transporter 1 (LAT1) and 4F2 c...
We have previously shown that the sodium-coupled neutral amino acid transporter, SNAT1, modulates NO production in pulmonary arterial endothelial cells (PAECs) from newborn piglets. Specifically, the ...
The objective of this study was to determine the effect of organic and inorganic Fe sources on the Fe absorption and gene expression of Fe and amino acid transporters in the ligated jejunal and ileal ...
Parkinson's disease (PD) is a frequently occurring condition that resulted from the loss of midbrain neurons, which synthesize the neurotransmitter dopamine. In this study, we established mouse models...
Apicomplexan parasites are auxotrophic for a range of amino acids which must be salvaged from their host cells, either through direct uptake or degradation of host proteins. Here, we describe a family...
The expression of transporters involved in bile acid homeostasis is differentially regulated during obstructive cholestasis. Bile acids are also substrates of the drug efflux transporter b...
The P-glycoprotein (P-gp) is a membranous transporter that modulates the intracellular concentrations of many drugs and plays thus a major role in the efficacy of the therapeutics that act...
This study of the tolerance and acceptability of an amino acid based feed will assess gastrointestinal (GI) tolerance, product intake and acceptability in relation to taste, smell, texture...
Protein requirements in individuals who participate in endurance-based exercise training have been suggested to be greater than the current recommended dietary allowance (RDA). The biolog...
The aim is to assess the impact of physical inactivity on muscle amino acid balance. In addition, we will evaluate how the diet and/or a pharmacological intervention designed to manipulate...
A high-affinity, low capacity system y+ amino acid transporter with strong similarity to CATIONIC AMINO ACID TRANSPORTER 1. The two isoforms of the protein, CAT-2A and CAT-2B, exist due to alternative mRNA splicing. The transporter has specificity for the transport of ARGININE; LYSINE; and ORNITHINE.
A pancreatic trypsin inhibitor common to all mammals. It is secreted with the zymogens into the pancreatic juice. It is a protein composed of 56 amino acid residues and is different in amino acid composition and physiological activity from the Kunitz bovine pancreatic trypsin inhibitor (APROTININ).
A high-affinity, low capacity system y+ amino acid transporter found ubiquitously. It has specificity for the transport of ARGININE; LYSINE; and ORNITHINE. It may also act as an ecotropic leukemia retroviral receptor.
A ubiquitous sodium-dependent neutral amino acid transporter. The preferred substrates for this transporter system include ALANINE; SERINE; and CYSTEINE.
A sodium-dependent neutral amino acid transporter that accounts for most of the sodium-dependent neutral amino acid uptake by mammalian cells. The preferred substrates for this transporter system include ALANINE; SERINE; and GLUTAMINE.
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...
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Hepatology is the study of liver, gallbladder, biliary tree, and pancreas, and diseases associated with them. This includes viral hepatitis, alcohol damage, cirrhosis and cancer. As modern lifestyles change, with alcoholism and cancer becoming more promi...