Advertisement

Central Regulation of Insulin Sensitivity

  • Silvana Obici
  • Rossetti Luciano

Abstract

Insulin rapidly lowers blood glucose levels via inhibition of endogenous glucose production and stimulation of glucose uptake. The mechanisms by which insulin modulates hepatic glucose production involve either activation of insulin signaling in hepatocytes (direct efects) or activation of insulin receptors in extra-hepatic sites (indirect effects), which in turn leads to inhibition of glucose production via neural and/or humoral mediators. The direct effects can be further divided into acute insulin action leading to rapid decrease in glucose production and chronic insulin action modulating the gene expression of rate-limiting enzymes within the biochemical pathways leading to glucose production. Short-term effects of insulin on hepatic glucose fluxes may be divided into three major components: (a) direct effects on the liver, mostly leading to rapid inhibition of glycogenolysis;1,2 (b) indirect effects mediated via peripheral actions of insulin, mostly modulating lipolysis;3, 4, 5, 6 (c) indirect effects mediated via activation of hypothalamic insulin signaling.7,8 Furthermore, insulin exerts potent long-term effects on liver gene expression and function.9. These more chronic actions of insulin can in turn markedly affect the acute responses to an increase in circulating insulin levels.10,11

Keywords

Insulin Action Glucose Production KATP Channel Arcuate Nucleus Hepatic Glucose Production 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sindelar DK, Chu CA, Neal DW et al. Interaction of equal increments in arterial and portal vein insulin on hepatic glucose production in the dog. Am J Physiol 1997; 273:E972–E980.PubMedGoogle Scholar
  2. 2.
    Sindelar DK, Chu CA, Venson P et al. Basal hepatic glucose production is regulated by the portal vein insulin concentration. Diabetes 1998; 47:523–529.PubMedGoogle Scholar
  3. 3.
    Boden G, Chen X, Capulong E et al. Effects of free fatty acids on gluconeogenesis and autoregulation of glucose production in type 2 diabetes. Diabetes 2001; 50:810–816.PubMedGoogle Scholar
  4. 4.
    Lewis GF, Vranic M, Harley P et al. Fatty acids mediate the acute extrahepatic effects of insulin on hepatic glucose production in humans. Diabetes 1997; 46:1111–1119.PubMedGoogle Scholar
  5. 5.
    Rebrin K, Steil GM, Getty L et al. Free fatty acid as a link in the regulation of hepatic glucose output by peripheral insulin. Diabetes 1995; 44:1038–1045.PubMedGoogle Scholar
  6. 6.
    Sindelar DK, Chu CA, Rohlie M et al. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 1997; 46:187–196.PubMedGoogle Scholar
  7. 7.
    Obici S, Zhang BB, Karkanias G et al. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med 2002; 8:1376–1382.PubMedGoogle Scholar
  8. 8.
    Pocai A, Lam TK, Gutierrez-Juarez R et al. Hypothalamic KATP channels control hepatic glucose production. Nature (In press).Google Scholar
  9. 9.
    Hornbuckle LA, Edgerton DS, Ayala JE et al. Selective tonic inhibition of G-6-Pase catalytic subunit, but not G-6-P transporter, gene expression by insulin in vivo. Am J Physiol Endocrinol Metab 2001; 281:E713–E725.PubMedGoogle Scholar
  10. 10.
    Fisher SJ, Kahn CR. Insulin signaling is required for insulin’s direct and indirect action on hepatic glucose production. J Clin Invest 2003; 111:463–468.PubMedGoogle Scholar
  11. 11.
    Michael MD, Kulkarni RN, Postic C et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 2000; 6:87–97.PubMedGoogle Scholar
  12. 12.
    Saltiel AR, Kahn CR. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414:799–806.PubMedGoogle Scholar
  13. 13.
    Cherrington AD. Banting Lecture 1997. Control of glucose uptake and release by the liver in vivo. Diabetes 1999; 48:1198–1214.PubMedGoogle Scholar
  14. 14.
    Consoli A, Nurjhan N, Capani F et al. Predominant role of gluconeogenesis in increased hepatic glucose production in NIDDM. Diabetes 1989; 38:550–557.PubMedGoogle Scholar
  15. 15.
    Ferrannini E, Galvan AQ, Gastaldelli A et al. Insulin: New roles for an ancient hormone. Eur J Clin Invest 1999; 29:842–852.PubMedGoogle Scholar
  16. 16.
    Magnusson I, Rothman DL, Gerard DP et al. Contribution of hepatic glycogenolysis to glucose production in humans in response to a physiological increase in plasma glucagon concentration. Diabetes 1995; 44:185–189.PubMedGoogle Scholar
  17. 17.
    Rothman DL, Magnusson I, Katz LD et al. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science 1991; 254:573–576.PubMedGoogle Scholar
  18. 18.
    Moller DE. New drug targets for type 2 diabetes and the metabolic syndrome. Nature 2001; 414:821–827.PubMedGoogle Scholar
  19. 19.
    Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000; 106:473–481.PubMedGoogle Scholar
  20. 20.
    Kopelman PG. Obesity as a medical problem. Nature 2000; 404:635–643.PubMedGoogle Scholar
  21. 21.
    Friedman JM. Obesity in the new millennium. Nature 2000; 404:632–634.PubMedGoogle Scholar
  22. 22.
    Kopelman PG, Hitman GA. Diabetes. Exploding type II. Lancet 1998; 352(Suppl 4):SIV5.PubMedGoogle Scholar
  23. 23.
    Porte D, Seeley RJ, Woods SC et al. Obesity, diabetes and the central nervous system. Diabetologia 1998; 41:863–881.PubMedGoogle Scholar
  24. 24.
    Obici S, Rossetti L. Minireview: Nutrient sensing and the regulation of insulin action and energy balance. Endocrinology 2003; 144:5172–5178.PubMedGoogle Scholar
  25. 25.
    Flier JS. Diabetes. The missing link with obesity? Nature 2001; 409:292–293.PubMedGoogle Scholar
  26. 26.
    Flier JS. Obesity wars: Molecular progress confronts an expanding epidemic. Cell 2004; 116:337–350.PubMedGoogle Scholar
  27. 27.
    Flegal KM, Carroll MD, Ogden CL et al. Prevalence and trends in obesity among US adults, 1999–2000. JAMA 2002; 288:1723–1727.PubMedGoogle Scholar
  28. 28.
    Combs TP, Berg AH, Obici S et al. Endogenous glucose production is inhibited by the adipose-derived protein Acrp30. J Clin Invest 2001; 108:1875–1881.PubMedGoogle Scholar
  29. 29.
    Rajala MW, Obici S, Scherer PE et al. Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest 2003; 111:225–230.PubMedGoogle Scholar
  30. 30.
    Rangwala SM, Rich AS, Rhoades B et al. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 2004; 53(8):1937–41.PubMedGoogle Scholar
  31. 31.
    Porte D, Baskin DG, Schwartz MW. Leptin and insulin action in the central nervous system. Nutr Rev 2002; 60:S20–S29.PubMedGoogle Scholar
  32. 32.
    Schwartz MW, Woods SC, Porte D et al. Central nervous system control of food intake. Nature 2000; 404:661–671.PubMedGoogle Scholar
  33. 33.
    Woods SC, Schwartz MW, Baskin DG et al. Food intake and the regulation of body weight. Annu Rev Psychol 2000; 51:255–277.PubMedGoogle Scholar
  34. 34.
    Ahima RS, Prabakaran D, Mantzoros C et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996; 382:250–252.PubMedGoogle Scholar
  35. 35.
    Gutierrez-Juarez R, Obici S, Rossetti L. Melanocortin-independent effects of leptin on hepatic glucose fluxes. J Biol Chem 2004; 279:49704–49715.PubMedGoogle Scholar
  36. 36.
    Schwartz MW, Sipols A, Kahn SE et al. Kinetics and specificity of insulin uptake from plasma into cerebrospinal fluid. Am J Physiol 1990; 259:E378–E383.PubMedGoogle Scholar
  37. 37.
    Gerozissis K, Rouch C, Nicolaidis S et al. Brain insulin response to feeding in the rat is both macronutrient and area specific. Physiol Behav 1998; 65:271–275.PubMedGoogle Scholar
  38. 38.
    Gerozissis K, Orosco M, Rouch C et al. Insulin responses to a fat meal in hypothalamic microdialysates and plasma. Physiol Behav 1997; 62:767–772.PubMedGoogle Scholar
  39. 39.
    Unger JW, Betz M. Insulin receptors and signal transduction proteins in the hypothalamo-hypophyseal system: A review on morphological findings and functional implications. Histol Histopathol. 1998; 13:1215–1224.PubMedGoogle Scholar
  40. 40.
    Marks JL, Porte D, Stahl WL et al. Localization of insulin receptor mRNA in rat brain by in situ hybridization. Endocrinology 1990; 127:3234–3236.PubMedGoogle Scholar
  41. 41.
    Baskin DG, Sipols AJ, Schwartz MW et al. Immunocytochemical detection of insulin receptor substrate-1 (IRS-1) in rat brain: Colocalization with phosphotyrosine. Regul Pept 1993; 48:257–266.PubMedGoogle Scholar
  42. 42.
    Woods SC, Seeley RJ, Porte D et al. Signals that regulate food intake and energy homeostasis. Science 1998; 280:1378–1383.PubMedGoogle Scholar
  43. 43.
    Woods DC, Lotter EC, McKay LD et al. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282:503–505.PubMedGoogle Scholar
  44. 44.
    Davis SN, Dunham B, Walmsley K et al. Brain of the conscious dog is sensitive to physiological changes in circulating insulin. Am J Physiol 1997; 272:E567–E575.PubMedGoogle Scholar
  45. 45.
    Davis SN, Colburn C, Dobbins R et al. Evidence that the brain of the conscious dog is insulin sensitive. J Clin Invest 1995; 95:593–602.PubMedGoogle Scholar
  46. 46.
    Richardson RD, Ramsay DS, Lernmark A et al. Weight loss in rats following intraventricular transplants of pancreatic islets. Am J Physiol 1994; 266:R59–R64.PubMedGoogle Scholar
  47. 47.
    Sipols AJ, Baskin DG, Schwartz MW. Effect of intracerebroventricular insulin infusion on diabetic hyperphagia and hypothalamic neuropeptide gene expression. Diabetes 1995; 44:147–151.PubMedGoogle Scholar
  48. 48.
    Schwartz MW, Marks JL, Sipols AJ et al. Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats. Endocrinology 1991; 128:2645–2647.PubMedCrossRefGoogle Scholar
  49. 49.
    Sahu A, Dube MG, Phelps CP et al. Insulin and insulin-like growth factor II suppress neuropeptide Y release from the nerve terminals in the paraventricular nucleus: A putative hypothalamic site for energy homeostasis. Endocrinology 1995; 136:5718–5724.PubMedGoogle Scholar
  50. 50.
    Liang C, Doherty JU, Faillace R et al. Insulin infusion in conscious dogs. Effects on systemic and coronary hemodynamics, regional blood flows, and plasma catecholamines. J Clin Invest 1982; 69:1321–1336.PubMedCrossRefGoogle Scholar
  51. 51.
    Rowe JW, Young JB, Minaker KL et al. Effect of insulin and glucose infusions on sympathetic nervous system activity in normal man. Diabetes 1981; 30:219–225.PubMedGoogle Scholar
  52. 52.
    Air EL, Strowski MZ, Benoit SC et al. Small molecule insulin mimetics reduce food intake and body weight and prevent development of obesity. Nat Med 2002; 8:179–183.PubMedGoogle Scholar
  53. 53.
    McGowan MK, Andrews KM, Grossman SP. Chronic intrahypothalamic infusions of insulin or insulin antibodies alter body weight and food intake in the rat. Physiol Behav 1992; 51:753–766.PubMedGoogle Scholar
  54. 54.
    Obici S, Feng Z, Karkanias G et al. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat Neurosci 2002; 5:566–572.PubMedGoogle Scholar
  55. 55.
    Bruning JC, Gautam D, Burks DJ et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000; 289:2122–2125.PubMedGoogle Scholar
  56. 56.
    Grill HJ, Schwartz MW, Kaplan JM et al. Evidence that the caudal brainstem is a target for the inhibitory effect of leptin on food intake. Endocrinology 2002; 143:239–246.PubMedGoogle Scholar
  57. 57.
    Spanswick D, Smith MA, Groppi VE et al. Leptin inhibits hypothalamic neurons by activation of ATP-sensitive potassium channels. Nature 1997; 390:521–525.PubMedGoogle Scholar
  58. 58.
    Spanswick D, Smith MA, Mirshamsi S et al. Insulin activates ATP-sensitive K+ channels in hypothalamic neurons of lean, but not obese rats. Nat Neurosci 2000; 3:757–758.PubMedGoogle Scholar
  59. 59.
    Wolkow CA, Kimura KD, Lee MS et al. Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 2000; 290:147–150.PubMedGoogle Scholar
  60. 60.
    Apfeld J, Kenyon C. Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell 1998; 95:199–210.PubMedGoogle Scholar
  61. 61.
    Matsuhisa M, Yamasaki Y, Shiba Y et al. Important role of the hepatic vagus nerve in glucose uptake and production by the liver. Metabolism 2000; 49:11–16.PubMedGoogle Scholar
  62. 62.
    Aguilar-Bryan L, Bryan J. Molecular biology of adenosine triphosphate-sensitive potassium channels. Endocr Rev 1999; 20:101–135.PubMedGoogle Scholar
  63. 63.
    Seino S, Miki T. Physiological and pathophysiological roles of ATP-sensitive K+ channels. Prog Biophys Mol Biol 2003; 81:133–176.PubMedGoogle Scholar
  64. 64.
    Magnuson MA. Tissue-specific regulation of glucokinase gene expression. J Cell Biochem 1992; 48:115–121.PubMedGoogle Scholar
  65. 65.
    Cowley MA, Smart JL, Rubinstein M et al. Leptin activates anorexigenic POMC neurons through a neural network in the arcuate nucleus. Nature 2001; 411:480–484.PubMedGoogle Scholar
  66. 66.
    Cowley MA, Pronchuk N, Fan W et al. Integration of NPY, AGRP, and melanocortin signals in the hypothalamic paraventricular nucleus: Evidence of a cellular basis for the adipostat. Neuron 1999; 24:155–163.PubMedGoogle Scholar
  67. 67.
    Klebig ML, Wilkinson JE, Geisler JG et al. Ectopic expression of the agouti gene in transgenic mice causes obesity, features of type II diabetes, and yellow fur. Proc Natl Acad Sci USA 1995; 92:4728–4732.PubMedGoogle Scholar
  68. 68.
    Butler AA, Cone RD. Knockout studies defining different roles for melanocortin receptors in energy homeostasis. Ann NY Acad Sci 2003; 994:240–245.PubMedGoogle Scholar
  69. 69.
    Butler AA, Kesterson RA, Khong K et al. A unique metabolic syndrome causes obesity in the melanocortin-3 receptor-deficient mouse. Endocrinology 2000; 141:3518–3521.PubMedGoogle Scholar
  70. 70.
    Huszar D, Lynch CA, Fairchild-Huntress V et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell 1997; 88:131–141.PubMedGoogle Scholar
  71. 71.
    Obici S, Feng Z, Tan, J et al. Central melanocortin receptors regulate insulin action. J Clin Invest 2001; 108:1079–1085.PubMedGoogle Scholar
  72. 72.
    Barzilai N, She L, Liu L et al. Decreased visceral adiposity accounts for leptin effect on hepatic but not peripheral insulin action. Am J Physiol 1999; 277:E291–E298.PubMedGoogle Scholar
  73. 73.
    Liu L, Karkanias GB, Morales JC et al. Intracerebroventricular leptin regulates hepatic but not peripheral glucose fluxes. J Biol Chem 1998; 273:31160–31167.PubMedGoogle Scholar
  74. 74.
    Fan W, Dinulescu DM, Butler AA et al. The central melanocortin system can directly regulate serum insulin levels. Endocrinology 2000; 141:3072–3079.PubMedGoogle Scholar
  75. 75.
    Halaas JL, Gajiwala KS, Maffei M et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269:543–546.PubMedGoogle Scholar
  76. 76.
    Halaas JL, Boozer C, Blair-West J et al. Physiological response to long-term peripheral and central leptin infusion in lean and obese mice. Proc Natl Acad Sci USA 1997; 94:8878–8883.PubMedGoogle Scholar
  77. 77.
    Shimomura I, Hammer RE, Ikemoto S et al. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999; 401:73–76.PubMedGoogle Scholar
  78. 78.
    Rossetti L, Massillon D, Barzilai N et al. Short term effects of leptin on hepatic gluconeogenesis and in vivo insulin action. J Biol Chem 1997; 272:27758–27763.PubMedGoogle Scholar
  79. 79.
    Bates SH, Stearns WH, Dundon TA et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature 2003; 421:856–859.PubMedGoogle Scholar
  80. 80.
    Niswender KD, Morrison CD, Clegg DJ et al. Insulin activation of phosphatidylinositol 3-kinase in the hypothalamic arcuate nucleus: A key mediator of insulin-induced anorexia. Diabetes 2003; 52:227–231.PubMedGoogle Scholar
  81. 81.
    Schwartz MW, Baskin DG, Bukowski TR et al. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 1996; 45:531–535.PubMedGoogle Scholar
  82. 82.
    Barzilai N, Wang J, Massilon D et al. Leptin selectively decreases visceral adiposity and enhances insulin action. J Clin Invest 1997; 100:3105–3110.PubMedGoogle Scholar
  83. 83.
    Muoio DM, Dohm GL, Fiedorek FT et al. Leptin directly alters lipid partitioning in skeletal muscle. Diabetes 1997; 46:1360–1363.PubMedGoogle Scholar
  84. 84.
    Muoio DM, Dohm GL, Tapscott EB et al. Leptin opposes insulin’s effects on fatty acid partitioning in muscles isolated from obese ob/ob mice. Am J Physiol 1999; 276:E913–E921.PubMedGoogle Scholar
  85. 85.
    Minokoshi Y, Kim YB, Peroni OD et al. Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase. Nature 2002; 415:339–343.PubMedGoogle Scholar
  86. 86.
    Balthasar N, Coppari R, McMinn J et al. Leptin receptor signaling in POMC neurons is required for normal body weight homeostasis. Neuron 2004; 42:983–991.PubMedGoogle Scholar
  87. 87.
    da Silva AA, Kuo JJ, Hall JE. Role of hypothalamic melanocortin 3/4-receptors in mediating chronic cardiovascular, renal, and metabolic actions of leptin. Hypertension 2004; 43:1312–1317.PubMedGoogle Scholar
  88. 88.
    Haynes WG, Morgan DA, Djalali A et al. Interactions between the melanocortin system and leptin in control of sympathetic nerve traffic. Hypertension 1999; 33:542–547.PubMedGoogle Scholar
  89. 89.
    Rahmouni K, Haynes WG, Morgan DA et al. Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci 2003; 23:5998–6004.PubMedGoogle Scholar
  90. 90.
    Muzumdar R, Ma X, Yang X et al. Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms. FASEB 2003; 17:1130–1132.Google Scholar
  91. 91.
    Zhao AZ, Shinohara MM, Huang D et al. Leptin induces insulin-like signaling that antagonizes cAMP elevation by glucagon in hepatocytes. J Biol Chem 2000; 275:11348–11354.PubMedGoogle Scholar
  92. 92.
    Lam NT, Lewis JT, Cheung AT et al. Leptin increases hepatic insulin sensitivity and protein tyrosine phosphatase 1B expression. Mol Endocrinol 2004; 28:1333–1345.Google Scholar
  93. 93.
    Huang W, Dedousis N, Bhatt BA et al. Impaired activation of phosphatidylinositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity. J Biol Chem 2004; 279:21695–21700.PubMedGoogle Scholar
  94. 94.
    Cohen P, Zhao C, Cai X et al. Selective deletion of leptin receptor in neurons leads to obesity. J Clin Invest 2001; 108:1113–1121.PubMedGoogle Scholar
  95. 95.
    Niswender KD, Morton GJ, Stearns WH, et al. Intracellular signalling. Key enzyme in leptin-induced anorexia. Nature 2001; 413:794–795.PubMedGoogle Scholar
  96. 96.
    Baskin DG, Figlewicz LD, Seeley RJ et al. Insulin and leptin: Dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res 1999; 848:114–123.PubMedGoogle Scholar
  97. 97.
    Schwartz MW, Figlewicz DP, Baskin DG et al. Insulin in the brain: A hormonal regulator of energy balance. Endocr Rev 1992; 13:387–414.PubMedGoogle Scholar
  98. 98.
    Seeley RJ, van Dijk G, Campfield LA et al. Intraventricular leptin reduces food intake and body weight of lean rats but not obese Zucker rats. Horm Metab Res 1996; 28:664–668.PubMedCrossRefGoogle Scholar
  99. 99.
    Wang J, Liu R, Hawkins M et al. A nutrient-sensing pathway regulates leptin gene expression in muscle and fat. Nature 1998; 393:684–688.PubMedGoogle Scholar
  100. 100.
    Levin BE, Dunn-Meynell AA, Routh VH. Brain glucose sensing and body energy homeostasis: Role in obesity and diabetes. Am J Physiol 1999; 276:R1223–R1231.PubMedGoogle Scholar
  101. 101.
    Miller JC, Gnaedinger JM, Rapaport SI. Utilization of plasma fatty acids in rat brain: Distribution of 14C-Palmitate between oxidative and synthetic pathways. J Neurochem 1987; 49:1507–1514.PubMedGoogle Scholar
  102. 102.
    Loftus TM, Jaworsky DE, Frehywot GL et al. Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000; 88:2379–2381.Google Scholar
  103. 103.
    Obici S, Feng Z, Arduini A et al. Inhibition of hypothalamic carnitine palmitoyltransferase-1 decreases food intake and glucose production. Nat Med 2003; 9:756–761.PubMedGoogle Scholar
  104. 104.
    Boden G, Chen X, Ruiz J et al. Mechanisms of fatty acid-induced inhibition of glucose uptake. J Clin Invest 1994; 93:2438–2446.PubMedGoogle Scholar
  105. 105.
    Lam TK, Pocai A, Gutierrez-Juarez R et al. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med 2005; 11:320–327.PubMedGoogle Scholar
  106. 106.
    Obici S, Feng Z, Morgan K et al. Central administration of oleic acid inhibits glucose production and food intake. Diabetes 2002; 51:271–275.PubMedGoogle Scholar
  107. 107.
    Morgan K, Obici S, Rossetti L. Hypothalamic responses to long-chain fatty acids are nutritionally regulated. J Biol Chem 2004; 279:31139–31148.PubMedGoogle Scholar

Copyright information

© Landes Bioscience and Springer Science+Business Media 2007

Authors and Affiliations

  • Silvana Obici
  • Rossetti Luciano
    • 1
  1. 1.Albert Einstein College of MedicineBronxUSA

Personalised recommendations