FGF19 action in the brain induces insulin-independent glucose lowering

Journal of Clinical Investigation

Volumn 123, Issue 11, 2013, Pages 4799-4808

  Morton, Gregory J ^a   Matsen, Miles E ^a   Bracy, Deanna P ^b   Meek, Thomas H ^a   Nguyen, Hong T ^a   Stefanovski, Darko ^c   Bergman, Richard N ^c   Wasserman, David H ^b   Schwartz, Michael W ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c CEDARS SINAI MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 TERT BUTYL 3 [6 (3,5 DIMETHOXYPHENYL) 2 (4 DIETHYLAMINOBUTYLAMINO)PYRIDO[2,3 D]PYRIMIDIN 7 YL]UREA; GLUCOSE; INSULIN; LACTIC ACID; RECOMBINANT FIBROBLAST GROWTH FACTOR 19; RECOMBINANT GROWTH FACTOR; UNCLASSIFIED DRUG;

ANIMAL EXPERIMENT; ANTIDIABETIC ACTIVITY; ARTICLE; BRAIN; BRAIN FUNCTION; CONTROLLED STUDY; DRUG EFFECT; DRUG POTENCY; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; INSULIN BLOOD LEVEL; INSULIN RELEASE; INSULIN SENSITIVITY; INTESTINE; INTRAVENOUS GLUCOSE TOLERANCE TEST; LOW DRUG DOSE; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE;

EID: 84887447664     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI70710     Document Type: Article

References (53)

1. Best JD, Kahn SE, Ader M, Watanabe RM, Ni TC, Bergman RN. Role of glucose effectiveness in the determination of glucose tolerance. Diabetes Care. 1996; 19(9):1018-1030.
2. Alonso LC, et al. Simultaneous measurement of insulin sensitivity, insulin secretion, and the disposition index in conscious unhandled mice. Obesity (Silver Spring). 2012;20(7):1403-1412.
3. Beenken A, Mohammadi M. The FGF family: biology, pathophysiology and therapy. Nat Rev Drug Discov. 2009;8(3):235-253.
4. Holt JA, et al. Definition of a novel growth factordependent signal cascade for the suppression of bile acid biosynthesis. Genes Dev. 2003;17(13):1581-1591.
5. Inagaki T, et al. Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis. Cell Metab. 2005;2(4):217-225.
6. Fu L, et al. Fibroblast growth factor 19 increases metabolic rate and reverses dietary and leptin-deficient diabetes. Endocrinology. 2004;145(6):2594-2603.
7. Tomlinson E, et al. Transgenic mice expressing human fibroblast growth factor-19 display increased metabolic rate and decreased adiposity. Endocrinology. 2002;143(5):1741-1747.
8. Kir S, et al. FGF19 as a postprandial, insulin-independent activator of hepatic protein and glycogen synthesis. Science. 2011;331(6024):1621-1624.
9. Huang X, Yang C, Luo Y, Jin C, Wang F, McKeehan WL. FGFR4 prevents hyperlipidemia and insulin resistance but underlies high-fat diet induced fatty liver. Diabetes. 2007;56(10):2501-2510.
10. Wu AL, et al. FGF19 regulates cell proliferation, glucose and bile acid metabolism via FGFR4-dependent and independent pathways. PLoS One. 2011; 6(3):e17868.
11. Wu AL, et al. Amelioration of type 2 diabetes by antibody-mediated activation of fibroblast growth factor receptor 1. Sci Transl Med. 2011; 3(113):113ra126.
12. Gonzalez AM, Berry M, Maher PA, Logan A, Baird A. A comprehensive analysis of the distribution of FGF-2 and FGFR1 in the rat brain. Brain Res. 1995; 701(1-2):201-226.
13. Matsuo A, et al. Immunohistochemical localization in the rat brain of an epitope corresponding to the fibroblast growth factor receptor-1. Neuroscience. 1994;60(1):49-66.
14. Ryan KK, Kohli R, Gutierrez-Aguilar R, Gaitonde SG, Woods SC, Seeley RJ. Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats. Endocrinology. 2013;154(1):9-15.
15. Lovejoy J, Newby FD, Gebhart SS, DiGirolamo M. Insulin resistance in obesity is associated with elevated basal lactate levels and diminished lactate appearance following intravenous glucose and insulin. Metabolism. 1992;41(1):22-27.
16. Ho JE, et al. Metabolic profiles during oral glucose glucose challenge. Diabetes. 2013;62(8):2689-2698.
17. Stefanovski D, et al. Estimating hepatic glucokinase activity using a simple model of lactate kinetics. Diabetes Care. 2012;35:1015-1020.
18. da Silva AA, do Carmo JM, Freeman JN, Tallam LS, Hall JE. A functional melanocortin system may be required for chronic CNS-mediated antidiabetic and cardiovascular actions of leptin. Diabetes. 2009; 58(8):1749-1756.
19. Berglund ED, et al. Direct leptin action on POMC neurons regulates glucose homeostasis and hepatic insulin sensitivity in mice. J Clin Invest. 2012; 122(3):1000-1009.
20. Hill JW, et al. Direct insulin and leptin action on proopiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metab. 2010; 11(4):286-297.
21. Konner AC, et al. Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab. 2007;5(6):438-449.
22. German JP, et al. Leptin action in the brain normalizes diabetic hyperglycemia via insulin-independent mechanisms. Endocrinology. 2011; 152(5):394-404.
23. Fujikawa T, Chuang JC, Sakata I, Ramadori G, Coppari R. Leptin therapy improves insulin-deficient type 1 diabetes by CNS-dependent mechanisms in mice. Proc Natl Acad Sci U S A. 2010; 107(40):17391-17396.
24. Hidaka S, et al. Chronic central leptin infusion restores hyperglycemia independent of food intake and insulin level in streptozotocin-induced diabetic rats. FASEB J. 2002;16(6):509-518.
25. Lin CY, Higginbotham DA, Judd RL, White BD. Central leptin increases insulin sensitivity in streptozotocin-induced diabetic rats. Am J Physiol Endocrinol Metab. 2002;282(5):E1084-E1091.
26. German JP, et al. Hypothalamic leptin signaling regulates hepatic insulin sensitivity via a neurocircuit involving the vagus nerve. Endocrinology. 2009; 150(10):4502-4511.
27. Lam TK, et al. Hypothalamic sensing of circulating fatty acids is required for glucose homeostasis. Nat Med. 2005;11(3):320-327.
28. Obici S, Feng Z, Morgan K, Stein D, Karkanias G, Rossetti L. Central administration of oleic acid inhibits glucose production and food intake. Diabetes. 2002;51(2):271-275.
29. Obici S, Zhang BB, Karkanias G, Rossetti L. Hypothalamic insulin signaling is required for inhibition of glucose production. Nat Med. 2002; 8(12):1376-1382.
30. Pocai A, et al. Hypothalamic K(ATP) channels control hepatic glucose production. Nature. 2005; 434(7036):1026-1031.
31. Kahn SE, et al. Exercise training delineates the importance of B-cell dysfunction to the glucose intolerance of human aging. J Clin Endocrinol Metab. 1992;74(6):1336-1342.
32. Lam CK, Chari M, Lam TK. CNS regulation of glucose homeostasis. Physiology (Bethesda). 2009; 24:159-170.
33. Morton GJ, Schwartz MW. Leptin and the central nervous system control of glucose metabolism. Physiol Rev. 2011;91(2):389-411.
34. D'Alessio DA, Kahn SE, Leusner CR, Ensinck JW. Glucagon-like peptide 1 enhances glucose tolerance both by stimulation of insulin release and by increasing insulin-independent glucose disposal. J Clin Invest. 1994;93(5):2263-2266.
35. Kahn SE, et al. Treatment with a somatostatin analog decreases pancreatic B-cell and whole body sensitivity to glucose. J Clin Endocrinol Metab. 1990; 71(4):994-1002.
36. Lam TK, Gutierrez-Juarez R, Pocai A, Rossetti L. Regulation of blood glucose by hypothalamic pyruvate metabolism. Science. 2005;309(5736):943-947.
37. Taniguchi A, et al. Insulin secretion, insulin sensitivity, and glucose effectiveness in nonobese individuals with varying degrees of glucose tolerance. Diabetes Care. 2000;23(1):127-128.
38. Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet. 1992;340(8825):925-929.
39. Felig P, Wahren J, Hendler R. Influence of oral glucose ingestion on splanchnic glucose and gluconeogenic substrate metabolism in man. Diabetes. 1975; 24(5):468-475.
40. Davis MA, Williams PE, Cherrington AD. Effect of a mixed meal on hepatic lactate and gluconeogenic precursor metabolism in dogs. Am J Physiol. 1984; 247(3 pt 1):E362-E369.
41. Davis MA, Williams PE, Cherrington AD. Net hepatic lactate balance following mixed meal feeding in the four-day fasted conscious dog. Metabolism. 1987; 36(9):856-862.
42. Brooks GA. Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise. Fed Proc. 1986;45(13):2924-2929.
43. DiGirolamo M, Newby FD, Lovejoy J. Lactate production in adipose tissue: a regulated function with extra-adipose implications. FASEB J. 1992; 6(7):2405-2412.
44. Potthoff MJ, et al. FGF15/19 regulates hepatic glucose metabolism by inhibiting the CREB-PGC-1alpha pathway. Cell Metab. 2011;13(6):729-738.
45. Kohli R, et al. Intestinal adaptation after ileal interposition surgery increases bile acid recycling and protects against obesity-related comorbidities. Am J Physiol Gastrointest Liver Physiol. 2010; 299(3):G652-G660.
46. Patti ME, et al. Serum bile acids are higher in humans with prior gastric bypass: potential contribution to improved glucose and lipid metabolism. Obesity (Silver Spring). 2009;17(9):1671-1677.
47. Jansen PL, et al. Alterations of hormonally active fibroblast growth factors after Roux-en-Y gastric bypass surgery. Dig Dis. 2011;29(1):48-51.
48. Pournaras DJ, et al. The role of bile after Roux-en-Y gastric bypass in promoting weight loss and improving glycaemic control. Endocrinology. 2012; 153(8):3613-3619.
49. Mingrone G, et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med. 2012;366(17):1577-1585.
50. Pinto S, et al. Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science. 2004; 304(5667):110-115.
51. Huszar D, et al. Targeted disruption of the melanocortin-4 receptor results in obesity in mice. Cell. 1997; 88:131-141.
52. Franklin B, Paxinos G. The Mouse Brain in Stereotaxic Coordinates. San Diego, California, USA: Academic Press; 1997.
53. Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes. 2006;55(2):390-397.