scholarly journals Amino acid transporters and nutrient-sensing mechanisms: new targets for treating insulin-linked disorders?

2007 ◽  
Vol 35 (5) ◽  
pp. 1215-1217 ◽  
Author(s):  
B. Reynolds ◽  
R. Laynes ◽  
M.H. Ögmundsdóttir ◽  
C.A.R. Boyd ◽  
D.C.I. Goberdhan
Keyword(s):  
Amino Acid ◽  
Normal Development ◽  
Nutrient Sensing ◽  
Amino Acid Transporters ◽  
Cancer Type ◽  
Growth Factor Signalling ◽  
In Vivo Analysis ◽  
Signalling Cascade

The IIS (insulin/IGF (insulin-like growth factor) signalling) cascade has an important role in regulating normal development and physiology, as evidenced by its effects in a host of major human diseases including cancer, Type 2 diabetes and neurodegeneration. Recently, it has become clear that multiple types of local nutrient-sensing mechanisms have an impact on cellular insulin-sensitivity through the downstream kinase TOR (target of rapamycin). In vivo analysis in flies has surprisingly highlighted PATs (proton-assisted amino acid transporters) as having a uniquely potent role in regulating IIS/TOR activity and growth, potentially via a novel signalling mechanism. Other molecules such as the heterodimeric amino acid transporter, CD98, which provides the principal route for cellular uptake of leucine, an amino acid implicated in regulating TOR, also appear to have important effects. As our understanding of how nutrient sensing has an impact on IIS/TOR increases, novel targets to modulate aberrant IIS in disease are likely to emerge, which could complement current strategies designed to block kinases in this pathway.

Hypoxic Stress Upregulates the Expression of Slc38a1 in Brown Adipocytes via Hypoxia-Inducible Factor-1α

Pharmacology ◽  
2017 ◽  
Vol 101 (1-2) ◽  
pp. 64-71 ◽  
Author(s):  
Tetsuhiro Horie ◽  
Kazuya Fukasawa ◽  
Takashi Iezaki ◽  
Gyujin Park ◽  
Yuki Onishi ◽  
...  
Keyword(s):  
Amino Acid ◽  
Hypoxia Inducible Factor ◽  
Amino Acid Transporters ◽  
Hypoxic Stress ◽  
Gene Encoding ◽  
Brown Adipocytes ◽  
Hypoxia Inducible Factor 1Α ◽  
Brown Adipose

The availability of amino acid in the brown adipose tissue (BAT) has been shown to be altered under various conditions; however, little is known about the possible expression and pivotal role of amino acid transporters in BAT under physiological and pathological conditions. The present study comprehensively investigated whether amino acid transporters are regulated by obesogenic conditions in BAT in vivo. Moreover, we investigated the mechanism underlying the regulation of the expression of amino acid transporters by various stressors in brown adipocytes in vitro. The expression of solute carrier family 38 member 1 (Slc38a1; gene encoding sodium-coupled neutral amino acid transporter 1) was preferentially upregulated in the BAT of both genetic and acquired obesity mice in vivo. Moreover, the expression of Slc38a1 was induced by hypoxic stress through hypoxia-inducible factor-1α, which is a master transcription factor of the adaptive response to hypoxic stress, in brown adipocytes in vitro. These results indicate that Slc38a1 is an obesity-associated gene in BAT and a hypoxia-responsive gene in brown adipocytes.

scholarly journals Inhibitors of the Neutral Amino Acid Transporters ASCT1 and ASCT2 Are Effective in In Vivo Models of Schizophrenia and Visual Dysfunction

2018 ◽  
Vol 367 (2) ◽  
pp. 292-301 ◽  
Author(s):  
Yong-Xin Li ◽  
Jia-Ying Yang ◽  
Miguel Alcantara ◽  
Grigor Abelian ◽  
Ashutosh Kulkarni ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neutral Amino Acid ◽  
Amino Acid Transporters ◽  
Visual Dysfunction ◽  
In Vivo Models

scholarly journals Mice Lacking the 68-Amino-Acid, Mammal-Specific N-Terminal Extension of WT1 Develop Normally and Are Fertile

2003 ◽  
Vol 23 (7) ◽  
pp. 2608-2613 ◽  
Author(s):  
Colin G. Miles ◽  
Joan Slight ◽  
Lee Spraggon ◽  
Maureen O'Sullivan ◽  
Charles Patek ◽  
...  
Keyword(s):  
Amino Acid ◽  
Translation Initiation ◽  
Histological Analysis ◽  
Normal Development ◽  
Wilms Tumor ◽  
Protein Isoforms ◽  
Translation Initiation Codon ◽  
Developing Kidney ◽  
Wt1 Protein

ABSTRACT Mutations in the Wilms' tumor 1 gene, WT1, cause pediatric nephroblastoma and the severe genitourinary disorders of Frasier and Denys-Drash syndromes. High levels of WT1 expression are found in the developing kidney, uterus, and testis—consistent with this finding, the WT1 knockout mouse demonstrates that WT1 is essential for normal genitourinary development. The WT1 gene encodes multiple isoforms of a zinc finger-containing protein by a combination of alternative splicing and alternative translation initiation. The use of an upstream, alternative CUG translation initiation codon specific to mammals results in the production of WT1 protein isoforms with a 68-amino-acid N-terminal extension. To determine the function in vivo of mammal-specific WT1 isoforms containing this extension, gene targeting was employed to introduce a subtle mutation into the WT1 gene. Homozygous mutant mice show a specific absence of the CUG-initiated WT1 isoforms yet develop normally to adulthood and are fertile. Detailed histological analysis revealed normal development of the genitourinary system.

scholarly journals CD98hc (SLC3A2) regulation of skin homeostasis wanes with age

2013 ◽  
Vol 210 (1) ◽  
pp. 173-190 ◽  
Author(s):  
Etienne Boulter ◽  
Soline Estrach ◽  
Aurélia Errante ◽  
Catherine Pons ◽  
Laurence Cailleteau ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Amino Acid ◽  
Molecular Mechanisms ◽  
Skin Aging ◽  
Amino Acid Transporters ◽  
Appreciable Effect ◽  
Nucleotide Exchange ◽  
Aged Skin

Skin aging is linked to reduced epidermal proliferation and general extracellular matrix atrophy. This involves factors such as the cell adhesion receptors integrins and amino acid transporters. CD98hc (SLC3A2), a heterodimeric amino acid transporter, modulates integrin signaling in vitro. We unravel CD98hc functions in vivo in skin. We report that CD98hc invalidation has no appreciable effect on cell adhesion, clearly showing that CD98hc disruption phenocopies neither CD98hc knockdown in cultured keratinocytes nor epidermal β1 integrin loss in vivo. Instead, we show that CD98hc deletion in murine epidermis results in improper skin homeostasis and epidermal wound healing. These defects resemble aged skin alterations and correlate with reduction of CD98hc expression observed in elderly mice. We also demonstrate that CD98hc absence in vivo induces defects as early as integrin-dependent Src activation. We decipher the molecular mechanisms involved in vivo by revealing a crucial role of the CD98hc/integrins/Rho guanine nucleotide exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis. Finally, we demonstrate that the deregulation of RhoA activation in the absence of CD98hc is also a result of impaired CD98hc-dependent amino acid transports.

Porcine circovirus type 2 affects the serum profile of amino acids and intestinal expression of amino acid transporters in mice

RSC Advances ◽  
2015 ◽  
Vol 5 (90) ◽  
pp. 73651-73659 ◽  
Author(s):  
Dingfu Xiao ◽  
Jie Yin ◽  
Wenkai Ren ◽  
Jianhua He ◽  
Xionggui Hu ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus Type 2 ◽  
Porcine Circovirus ◽  
Amino Acid Transporters ◽  
Highly Pathogenic ◽  
Serum Amino Acids ◽  
Amino Acids Profile

PCV2 is highly pathogenic, however, its effect on the serum amino acids profile is unknown.

scholarly journals Boramino acid as a marker for amino acid transporters

2015 ◽  
Vol 1 (8) ◽  
pp. e1500694 ◽  
Author(s):  
Zhibo Liu ◽  
Haojun Chen ◽  
Kai Chen ◽  
Yihan Shao ◽  
Dale O. Kiesewetter ◽  
...  
Keyword(s):  
Amino Acid ◽  
Animal Studies ◽  
Cell Uptake ◽  
Great Promise ◽  
Amino Acid Transporters ◽  
New Class ◽  
Mental Diseases ◽  
Imaging Probes ◽  
Specific Accumulation

Amino acid transporters (AATs) are a series of integral channels for uphill cellular uptake of nutrients and neurotransmitters. Abnormal expression of AATs is often associated with cancer, addiction, and multiple mental diseases. Although methods to evaluate in vivo expression of AATs would be highly useful, efforts to develop them have been hampered by a lack of appropriate tracers. We describe a new class of AA mimics—boramino acids (BAAs)—that can serve as general imaging probes for AATs. The structure of a BAA is identical to that of the corresponding natural AA, except for an exotic replacement of the carboxylate with -BF3−. Cellular studies demonstrate strong AAT-mediated cell uptake, and animal studies show high tumor-specific accumulation, suggesting that BAAs hold great promise for the development of new imaging probes and smart AAT-targeting drugs.

Probiotic reduced the impact of phthalates and bisphenol A mixture on type 2 diabetes mellitus development: merging bioinformatics with in vivo analysis

2021 ◽  
pp. 112325
Author(s):  
Katarina Baralić ◽  
Katarina Živančević ◽  
Dragica Jorgovanović ◽  
Dragana Javorac ◽  
Jelena Radovanović ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Bisphenol A ◽  
In Vivo Analysis ◽  
The Impact
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