181-OR: Amino Acid-Stimulated Alpha Cell Proliferation Requires Glutaminase Activity

Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 181-OR
Author(s):  
WALTER SIV ◽  
KATELYN SELLICK ◽  
AUSTIN REUTER ◽  
MATTHEW SHOU ◽  
JADE STANLEY ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Alpha Cell ◽  
Glutaminase Activity

198-OR: Role for the Cationic Amino Acid Transporter Slc7a2 in Alpha-Cell Proliferation and Islet Hormone Secretion

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 198-OR
Author(s):  
ERICK SPEARS ◽  
MATTHEW SHOU ◽  
WALTER A. SIV ◽  
CHUNHUA DAI ◽  
WENBIAO CHEN ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Hormone Secretion ◽  
Amino Acid Transporter ◽  
Alpha Cell ◽  
Cationic Amino Acid Transporter ◽  
Cationic Amino Acid ◽  
Islet Hormone ◽  
Acid Transporter

scholarly journals Branched-chain amino acids sustain pancreatic cancer growth by regulating lipid metabolism

2019 ◽  
Vol 51 (11) ◽  
pp. 1-11 ◽  
Author(s):  
Ji Hyeon Lee ◽  
Young-ra Cho ◽  
Ji Hye Kim ◽  
Jongwook Kim ◽  
Hae Yun Nam ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Cell Proliferation ◽  
Fatty Acid ◽  
Amino Acid ◽  
Metabolic Pathway ◽  
Cancer Growth ◽  
Pdac Cell ◽  
Growth And Survival ◽  
Branched Chain Amino Acid ◽  
Branched Chain

AbstractBranched-chain amino acid (BCAA) catabolism and high levels of enzymes in the BCAA metabolic pathway have recently been shown to be associated with cancer growth and survival. However, the precise roles of BCAA metabolism in cancer growth and survival remain largely unclear. Here, we found that BCAA metabolism has an important role in human pancreatic ductal adenocarcinoma (PDAC) growth by regulating lipogenesis. Compared with nontransformed human pancreatic ductal (HPDE) cells, PDAC cells exhibited significantly elevated BCAA uptake through solute carrier transporters, which were highly upregulated in pancreatic tumor tissues compared with normal tissues. Branched-chain amino-acid transaminase 2 (BCAT2) knockdown markedly impaired PDAC cell proliferation, but not HPDE cell proliferation, without significant alterations in glutamate or reactive oxygen species levels. Furthermore, PDAC cell proliferation, but not HPDE cell proliferation, was substantially inhibited upon knockdown of branched-chain α-keto acid dehydrogenase a (BCKDHA). Interestingly, BCKDHA knockdown had no significant effect on mitochondrial metabolism; that is, neither the level of tricarboxylic acid cycle intermediates nor the oxygen consumption rate was affected. However, BCKDHA knockdown significantly inhibited fatty-acid synthesis, indicating that PDAC cells may utilize BCAAs as a carbon source for fatty-acid biosynthesis. Overall, our findings show that the BCAA metabolic pathway may provide a novel therapeutic target for pancreatic cancer.

scholarly journals minidiscs encodes a putative amino acid transporter subunit required non-autonomously for imaginal cell proliferation

2000 ◽  
Vol 92 (2) ◽  
pp. 155-167 ◽  
Author(s):  
Jennifer F Martin ◽  
Evelyn Hersperger ◽  
Amanda Simcox ◽  
Allen Shearn
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Amino Acid Transporter ◽  
Acid Transporter

scholarly journals MicroRNA-126-3p Inhibits Angiogenic Function of Human Lung Microvascular Endothelial Cells via LAT1 (L-Type Amino Acid Transporter 1)-Mediated mTOR (Mammalian Target of Rapamycin) Signaling

2020 ◽  
Vol 40 (5) ◽  
pp. 1195-1206 ◽  
Author(s):  
Danting Cao ◽  
Andrew M. Mikosz ◽  
Alexandra J. Ringsby ◽  
Kelsey C. Anderson ◽  
Erica L. Beatman ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Amino Acid ◽  
Cell Apoptosis ◽  
Human Lung ◽  
Mammalian Target Of Rapamycin ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Objective: MicroRNA-126-3p (miR-126) is required for angiogenesis during organismal development or the repair of injured arterial vasculature. The role of miR-126 in lung microvascular endothelial cells, which are essential for gas exchange and for lung injury repair and regeneration, remains poorly understood. Considering the significant heterogeneity of endothelial cells from different vascular beds, we aimed to determine the role of miR-126 in regulating lung microvascular endothelial cell function and to elucidate its downstream signaling pathways. Approach and Results: Overexpression and knockdown of miR-126 in primary human lung microvascular endothelial cells (HLMVEC) were achieved via transfections of miR-126 mimics and antisense inhibitors. Increasing miR-126 levels in HLMVEC reduced cell proliferation, weakened tube formation, and increased cell apoptosis, whereas decreased miR-126 levels stimulated cell proliferation and tube formation. Whole-genome RNA sequencing revealed that miR-126 was associated with an antiangiogenic and proapoptotic transcriptomic profile. Using validation assays and knockdown approaches, we identified that the effect of miR-126 on HLMVEC angiogenesis was mediated by the LAT1 (L-type amino acid transporter 1), via regulation of mTOR (mammalian target of rapamycin) signaling. Furthermore, downregulation of miR-126 in HLMVEC inhibited cell apoptosis and improved endothelial tube formation during exposure to environmental insults such as cigarette smoke. Conclusions: miR-126 inhibits HLMVEC angiogenic function by targeting the LAT1-mTOR signaling axis, suggesting that miR-126 inhibition may be useful for conditions associated with microvascular loss, whereas miR-126 augmentation may help control unwanted microvascular angiogenesis.

scholarly journals The importance of serine metabolism in cancer

2016 ◽  
Vol 214 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Katherine R. Mattaini ◽  
Mark R. Sullivan ◽  
Matthew G. Vander Heiden
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Cancer Cells ◽  
De Novo ◽  
Redox Homeostasis ◽  
Cancer Cell Proliferation ◽  
Acid Transport ◽  
Nucleotide Synthesis ◽  
Serine Metabolism

Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer.

scholarly journals Molecular characterization of hNRP, a cDNA encoding a human nucleosome-assembly-protein-I-related gene product involved in the induction of cell proliferation

1994 ◽  
Vol 297 (2) ◽  
pp. 389-397 ◽  
Author(s):  
H U Simon ◽  
G B Mills ◽  
M Kozlowski ◽  
D Hogg ◽  
D Branch ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Gene Product ◽  
Thymidine Incorporation ◽  
Structural Features ◽  
Nucleosome Assembly ◽  
Proliferating Cells ◽  
Amino Acid Similarity ◽  
Nucleosome Assembly Protein

We have isolated from a human thymus cDNA library a cDNA clone encoding a potential protein with 54% amino acid similarity to that encoded by a previously identified cDNA for yeast nucleosome assembly protein I (NAP-I). The deduced amino acid sequence for this newly identified cDNA, designated hNRP (human NAP-related protein), contains a potential seven-residue nuclear localization motif, three clusters of highly acidic residues and other structural features found in various proteins implicated in chromatin formation. When expressed as a fusion protein in Escherichia coli, hNRP reacted specifically with a monoclonal antibody raised against human NAP-I. The hNRP transcript was detected in all tissues and cell lines studied, but levels were somewhat increased in rapidly proliferating cells. Moreover, levels of both hNRP mRNA and protein increased rapidly in cultured T-lymphocytes induced to proliferate by incubation with phorbol ester and ionomycin. Phorbol 12-myristate 13-acetate/ionomycin-induced increases in both hNRP mRNA and mitogenesis, as measured by thymidine incorporation, were markedly inhibited, however, in cells treated with an hNRP antisense oligonucleotide. These results demonstrate a correlation between induction of hNRP expression and mitogenesis and taken together with the structural similarities between hNRP and yeast NAP-I suggest that the hNRP gene product participates in DNA replication and thereby plays an important role in the process of cell proliferation.

FLUCTUATIONS OF ALPHA CELL CALCIUM, POTASSIUM AND SODIUM DURING AMINO ACID PERIFUSION OF RAT PANCREATIC ISLETS

Endocrinology ◽  
1987 ◽  
Vol 121 (1) ◽  
pp. 429-431 ◽  
Author(s):  
R. K. Kalkhoff ◽  
D. E. Yorde ◽  
R. J. Roman ◽  
K. A. Siegesmund ◽  
R. F. Dragen
Keyword(s):  
Amino Acid ◽  
Pancreatic Islets ◽  
Alpha Cell ◽  
Rat Pancreatic Islets ◽  
Cell Calcium

scholarly journals Nucleobindin-2 Is a Positive Modulator of EGF-Dependent Signals Leading to Enhancement of Cell Growth and Suppression of Adipocyte Differentiation

Endocrinology ◽  
2012 ◽  
Vol 153 (7) ◽  
pp. 3308-3319 ◽  
Author(s):  
Yuko Tagaya ◽  
Atsuko Miura ◽  
Shuichi Okada ◽  
Kihachi Ohshima ◽  
Masatomo Mori
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Calcium Binding ◽  
Egf Receptor ◽  
Adipocyte Differentiation ◽  
Proteolytic Processing ◽  
Receptor Internalization ◽  
Egf Receptors ◽  
Mapk Kinase ◽  
Amino Terminal

Nucleobindin-2 is a 420-amino-acid EF-hand calcium-binding protein that undergoes proteolytic processing to generate an 82-amino-acid amino-terminal peptide termed nesfatin-1. To determine whether nucleobindin-2 has any biological function, nucleobindin-2 was either overexpressed or knocked down by short hairpin RNA in cultured CHO cells expressing the human insulin and epidermal growth factor (EGF) receptors (CHO/IE) and in 3T3-L1 cells. Reduction in nucleobindin-2 expression inhibited EGF-stimulated MAPK kinase (S217/S221) and Erk phosphorylation (T202/Y204). In contrast, there was no significant effect on EGF-stimulated EGF receptor phosphorylation, EGF receptor internalization, or 52-kDa Shc and c-Raf phosphorylation. Although kinase suppressor of Ras-1 and protein phosphatase 2A expression was not changed, intracellular calcium concentrations and PP2A activity was significantly increased in nucleobindin-2 knocked-down cells. Concomitant with these alterations in EGF-stimulated signaling, cell proliferation was significantly reduced in nucleobindin-2 knocked-down cells. Moreover, reduced nucleobindin-2 expression in 3T3-L1 preadipocytes resulted in a greater extent of 3T3-L1 cell adipocyte differentiation. Taken together, these data indicate that nucleobindin-2 regulates EGF-stimulated MAPK kinase/Erk signaling, cell proliferation, and adipocyte differentiation.

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