Editing Valine (section)

== Medical significance ==

=== Metabolic diseases ===
The degradation of valine is impaired in the following [[Metabolic disorder|metabolic diseases]]:{{cn|date=October 2024}}

* [[Combined malonic and methylmalonic aciduria]] (CMAMMA)
* [[Maple syrup urine disease]] (MSUD)
* [[Methylmalonic acidemia]]
* [[Propionic acidemia]]

=== Insulin resistance ===
Lower levels of serum valine, like other branched-chain amino acids, are associated with weight loss and decreased [[insulin resistance]]: higher levels of valine are observed in the blood of diabetic mice, rats, and humans.<ref>{{cite journal | vauthors = Lynch CJ, Adams SH | title = Branched-chain amino acids in metabolic signalling and insulin resistance | journal = Nature Reviews. Endocrinology | volume = 10 | issue = 12 | pages = 723–36 | date = December 2014 | pmid = 25287287 | pmc = 4424797 | doi = 10.1038/nrendo.2014.171 }}</ref> Mice fed a BCAA-deprived diet for one day had improved insulin sensitivity, and feeding of a valine-deprived diet for one week significantly decreases blood glucose levels.<ref>{{cite journal | vauthors = Xiao F, Yu J, Guo Y, Deng J, Li K, Du Y, Chen S, Zhu J, Sheng H, Guo F | display-authors = 6 | title = Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice | journal = Metabolism | volume = 63 | issue = 6 | pages = 841–50 | date = June 2014 | pmid = 24684822 | doi = 10.1016/j.metabol.2014.03.006 }}</ref> In diet-induced obese and insulin resistant mice, a diet with decreased levels of valine and the other branched-chain amino acids resulted in a rapid reversal of the adiposity and an improvement in glucose-level control.<ref>{{cite journal | vauthors = Cummings NE, Williams EM, Kasza I, Konon EN, Schaid MD, Schmidt BA, Poudel C, Sherman DS, Yu D, Arriola Apelo SI, Cottrell SE, Geiger G, Barnes ME, Wisinski JA, Fenske RJ, Matkowskyj KA, Kimple ME, Alexander CM, Merrins MJ, Lamming DW | display-authors = 6 | title = Restoration of metabolic health by decreased consumption of branched-chain amino acids | journal = The Journal of Physiology | volume = 596 | issue = 4 | pages = 623–645 | date = February 2018 | pmid = 29266268 | pmc = 5813603 | doi = 10.1113/JP275075 }}</ref> The valine catabolite [[3-Hydroxyisobutyric acid|3-hydroxyisobutyrate]] promotes insulin resistance in mice by stimulating fatty acid uptake into muscle and lipid accumulation.<ref>{{cite journal | vauthors = Jang C, Oh SF, Wada S, Rowe GC, Liu L, Chan MC, Rhee J, Hoshino A, Kim B, Ibrahim A, Baca LG, Kim E, Ghosh CC, Parikh SM, Jiang A, Chu Q, Forman DE, Lecker SH, Krishnaiah S, Rabinowitz JD, Weljie AM, Baur JA, Kasper DL, Arany Z | display-authors = 6 | title = A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance | journal = Nature Medicine | volume = 22 | issue = 4 | pages = 421–6 | date = April 2016 | pmid = 26950361 | pmc = 4949205 | doi = 10.1038/nm.4057 }}</ref> In mice, a BCAA-restricted diet decreased fasting blood glucose levels and improved body composition.<ref>{{cite journal | vauthors = Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW | display-authors = 6 | title = Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health | journal = Cell Reports | volume = 16 | issue = 2 | pages = 520–530 | date = July 2016 | pmid = 27346343 | pmc = 4947548 | doi = 10.1016/j.celrep.2016.05.092 }}</ref>

=== Hematopoietic stem cells ===
Dietary valine is essential for [[hematopoietic stem cell]] (HSC) self-renewal, as demonstrated by experiments in mice.<ref>{{cite journal | vauthors = Taya Y, Ota Y, Wilkinson AC, Kanazawa A, Watarai H, Kasai M, Nakauchi H, Yamazaki S | display-authors = 6 | title = Depleting dietary valine permits nonmyeloablative mouse hematopoietic stem cell transplantation | journal = Science | volume = 354 | issue = 6316 | pages = 1152–1155 | date = December 2016 | pmid = 27934766 | doi = 10.1126/science.aag3145 | s2cid = 45815137 | bibcode = 2016Sci...354.1152T }}</ref> Dietary valine restriction selectively depletes long-term repopulating HSC in mouse bone marrow. Successful stem cell transplantation was achieved in mice without irradiation after 3 weeks on a valine restricted diet. Long-term survival of the transplanted mice was achieved when valine was returned to the diet gradually over a 2-week period to avoid [[refeeding syndrome]].