IRIG: Recent papers on insulin resistance
09/24/2011 18:05
Molecular mechanism of insulin resistance remains as
a hot topic in the main steam publications such as
those in CNS journals (Cell, Nature, Science). Papers
in the past few months suggest progress in multiple
aspects in the molecular connection between energy
surplus and insulin resistance. Here are examples:
Lipid is shown to induce ER stress through
interfering calcium homeostasis in liver (1),
phosphatidylcholine pathway is shown to have
anti-diabetic effects (2), MicroRNA 103/107
contributes to insulin resistance in obese mice (3),
Notch (4) and ER stress (5) impair insulin
sensitivity through FoxO1 activation, amino acids
contributes to insulin resistance in human based on
metabolomics analysis (6), B lymphocytes (7) and
eosinophils (8) join the inflammatory response to
regulate insulin sensitivity, PPARγ
acts in brain
to control insulin sensitivity and energy metabolism
(9), gut flora controls risk for cardiovascular
disease through phosphatidylcholine (10), FGF19 is
another FGF member with metabolic activity in liver
(11). Those basic studies may lead to
identification of new drug targets. However, a big
gap remains between those observations and
translational practice. Cited papers are listed
below.
Reference:
1. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, Hotamisligil GS: Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 2011;473:528-531
2. Lee JM, Lee YK, Mamrosh JL, Busby SA, Griffin PR, Pathak MC, Ortlund EA, Moore DD: A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects. Nature 2011;474:506-510
3. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M: MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 2011;474:649-653
4. Pajvani UB, Shawber CJ, Samuel VT, Birkenfeld AL, Shulman GI, Kitajewski J, Accili D: Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nature medicine 2011;17:961-967
5. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, Fisher SJ, White MF, Biddinger SB, Ozcan U: Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nature medicine 2011;17:356-365
6. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE: Metabolite profiles and the risk of developing diabetes. Nature medicine 2011;17:448-453
7. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG: B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature medicine 2011;17:610-617
8. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM: Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011;332:243-247
9. Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G, Nalbandian S, Fan W, Gayen JR, Mahata SK, Webster NJ, Schwartz MW, Olefsky JM: Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nature medicine 2011;17:618-622
10. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-63
11. Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ: FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 2011;331:1621-1624
By Jim
-----------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763-3163
E-mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
Reference:
1. Fu S, Yang L, Li P, Hofmann O, Dicker L, Hide W, Lin X, Watkins SM, Ivanov AR, Hotamisligil GS: Aberrant lipid metabolism disrupts calcium homeostasis causing liver endoplasmic reticulum stress in obesity. Nature 2011;473:528-531
2. Lee JM, Lee YK, Mamrosh JL, Busby SA, Griffin PR, Pathak MC, Ortlund EA, Moore DD: A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects. Nature 2011;474:506-510
3. Trajkovski M, Hausser J, Soutschek J, Bhat B, Akin A, Zavolan M, Heim MH, Stoffel M: MicroRNAs 103 and 107 regulate insulin sensitivity. Nature 2011;474:649-653
4. Pajvani UB, Shawber CJ, Samuel VT, Birkenfeld AL, Shulman GI, Kitajewski J, Accili D: Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nature medicine 2011;17:961-967
5. Zhou Y, Lee J, Reno CM, Sun C, Park SW, Chung J, Fisher SJ, White MF, Biddinger SB, Ozcan U: Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction. Nature medicine 2011;17:356-365
6. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE: Metabolite profiles and the risk of developing diabetes. Nature medicine 2011;17:448-453
7. Winer DA, Winer S, Shen L, Wadia PP, Yantha J, Paltser G, Tsui H, Wu P, Davidson MG, Alonso MN, Leong HX, Glassford A, Caimol M, Kenkel JA, Tedder TF, McLaughlin T, Miklos DB, Dosch HM, Engleman EG: B cells promote insulin resistance through modulation of T cells and production of pathogenic IgG antibodies. Nature medicine 2011;17:610-617
8. Wu D, Molofsky AB, Liang HE, Ricardo-Gonzalez RR, Jouihan HA, Bando JK, Chawla A, Locksley RM: Eosinophils sustain adipose alternatively activated macrophages associated with glucose homeostasis. Science 2011;332:243-247
9. Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G, Nalbandian S, Fan W, Gayen JR, Mahata SK, Webster NJ, Schwartz MW, Olefsky JM: Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nature medicine 2011;17:618-622
10. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL: Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 2011;472:57-63
11. Kir S, Beddow SA, Samuel VT, Miller P, Previs SF, Suino-Powell K, Xu HE, Shulman GI, Kliewer SA, Mangelsdorf DJ: FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science 2011;331:1621-1624
By Jim
-----------------------------
Jianping Ye, MD
Professor of Molecular Biology
Pennington Biomedical Research Center
Louisiana State University System
6400 Perkins Road
Baton Rouge, LA 70808
Phone: (225)763-3163
E-mail: yej@pbrc.edu
Webpage: http://labs.pbrc.edu/generegulation/index.htm
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