Nutritional influences on gut hormone release

Current Opinion in Endocrinology and Diabetes

Volumn 13, Issue 1, 2006, Pages 42-48

  Frost, Gary ^a   Brynes, Audrey E ^a   Ellis, Sandra ^a   Milton, Joanne E ^a   Nematy, Mohsen ^a   Philippou, Elena ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

Appetite regulation; Cholecystokinin; Ghrelin; Glucagon like peptide 1; Gut hormone; Peptide YY

Indexed keywords

BILE SALT; CHOLECYSTOKININ; ESTERASE INHIBITOR; FATTY ACID; FRUCTOSE; GALACTOSE; GASTROINTESTINAL HORMONE; GHRELIN; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; GUAR GUM; GUM ARABIC; ISPAGULA; LONG CHAIN FATTY ACID; MONOUNSATURATED FATTY ACID; OLIVE OIL; OMEGA 3 FATTY ACID; PECTIN; PEPTIDE YY; POLYUNSATURATED FATTY ACID; PROPIONATE SODIUM; PROPIONIC ACID DERIVATIVE; SATURATED FATTY ACID; SHORT CHAIN FATTY ACID; SUNFLOWER OIL; TRIACYLGLYCEROL; TRIACYLGLYCEROL LIPASE; TRYPSIN INHIBITOR; UNCLASSIFIED DRUG; UNINDEXED DRUG; UNSATURATED FATTY ACID;

BODY WEIGHT; DEVELOPED COUNTRY; DEVELOPING COUNTRY; DRUG EFFICACY; DRUG POTENCY; FAT INTAKE; FOOD INTAKE; GASTROINTESTINAL TRACT; HORMONE RELEASE; HUMAN; HUNGER; ISCHEMIC HEART DISEASE; LIPID DIET; LOW DRUG DOSE; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; NUTRIENT; NUTRIENT LOADING; NUTRITION; OBESITY; PROTEIN DIET; REVIEW; STOMACH EMPTYING;

EID: 33646944099     PISSN: 10683097     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.med.0000199007.34262.2b     Document Type: Review

References (91)

1. Wynne K, Stanley S, McGowan B, Bloom S. Appetite control. J Endocrinol 2005; 184:291-318.
2. Cummings DE, Purnell JQ, Frayo RS, et al. A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 2001; 50:1714-1719.
3. Tsohop M, Smiley DL, Heiman ML. Ghrelin induces adiposity in rodents. Nature 2000; 407:908-913.
4. Shiiya T, Nakazato M, Mizuta M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002; 87:240-244.
5. Callahan HS, Cummings DE, Pepe MS, et al. Postprandial suppression of plasma ghrelin level is proportional to ingested caloric load but does not predict intermeal intermeal interval in humans. J Clin Endocrinol Metab 2003; 89:1319-1324.
6. Arosio M, Ronchi CL, Beck-Peccoz P, et al. Effects of modified sham feeding on ghrelin levels in healthy human subjects. J Clin Endocrinol Metab 2004; 89:5101-5104. This study demonstrates that in normal-weight humans circulating ghrelin levels decrease after both actual and sham feedings, thereby highlighting the role of vagal activity in the control of ghrelin secretion.
7. Le Roux CW, Patterson M, Vincent RP, et al. Postprandial plasma ghrelin is suppressed proportional to meal calorie content in normal-weight but not obese subjects. J Clin Endocrinol Metab 2005; 90:1068-1071.
8. Caixas A, Bashore C, Nash W, et al. Insulin, unlike food intake, does not suppress ghrelin in human subjects. J Clin Endocrinol Metab 2002; 87:1902.
9. Williams DL, Cummings DE, Grill HJ, Kaplan JM. Meal-related ghrelin suppression requires postgastric feedback. Endocrinology 2003; 144:2765-2767.
10. Nakagawa E, Nagaya N, Okumura H, et al. Hyperglycaemia suppresses the secretion of ghrelin, a novel growth-hormone-releasing peptide: responses to the intravenous and oral administration of glucose. Clin Sci (Lond) 2002; 103:325-328.
11. Nakai Y, Hosoda H, Nin K, et al. Plasma levels of active form of ghrelin during oral glucose tolerance test in patients with anorexia nervosa. Eur J Endocrinol 2003; 149:R1-R3.
12. Mohlig M, Spranger J, Otto B, et al. Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans. J Endocrinol Invest 2002; 25:RC36-RC38.
13. Briatore L, Andraghetti G, Cordera R. Acute plasma glucose increase, but not early insulin response, regulates plasma ghrelin. Eur J Endocrinol 2003; 149:403-406.
14. Gottero C, Bellone S, Rapa A, et al. Standard light breakfast inhibits circulating ghrelin level to the same extent of oral glucose load in humans, despite different impact on glucose and insulin levels. J Endocrinol Invest 2003; 26:1203-1207.
15. Greenman Y, Golani N, Gilad S, et al. Ghrelin secretion is modulated in a nutrient- and gender-specific manner. Clin Endocrinol (Oxford) 2004; 60:382-388.
16. Schaller G, Schmidt A, Pleiner J, et al. Plasma ghrelin concentrations are not regulated by glucose or insulin. Diabetes 2003; 52:16-20.
17. Moesgaard SG, Ahrén B, Carr RD, et al. Effects of high-fat feeding and fasting on ghrelin expression in the mouse stomach. Regul Pept 2004; 120:261-267. In this study, C57BL/6J mice were used to show that ghrelin is expressed in the corpus and antrum of the stomach. Mice fed high-fat diets, leading to obesity and glucose intolerance, had a reduced number of ghrelin-producing cells compared with low-fat-fed mice. Moreover, fasting had no effect on ghrelin expression. The findings suggest ghrelin's role in the long-term control of feeding.
18. Teff KL, Elliott SS, Tschop M, et al. Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. J Clin Endocrinol Metab 2004; 89:2963-2972.
19. Erdmann J, Lippl F, Schusdziarra V. Differential effect of protein and fat on plasma ghrelin levels in man. Regul Pept 2003; 116:101-107.
20. Blom WAM, Stafleu A, de Craaf C, et al. Ghrelin response to carbohydrate-enriched breakfast is related to insulin. Am J Clin Nutr 2005; 81:367-375. The strength of this study was its double-blind randomized, cross-over design. Twenty men were studied for 4 h after the consumption of liquid breakfast meals of different energy and carbohydrate contents. Ghrelin levels were correlated with subjective measures of appetite and insulin levels, but less so with glucose concentrations, suggesting a direct or indirect regulation of ghrelin by insulin.
21. Monteleone P, Bencivenga R, Longobardi N, et al. Differential responses of circulating ghrelin to high-fat or high-carbohydrate meal in healthy women. J Clin Endocrinol Metab 2003; 88:5510-5514.
22. Weigle DS, Cummings DE, Newby PD, et al. Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J Clin Endocrinol Metab 2003; 88:1577-1586.
23. Nedvidkova J, Krykorkova I, Bartak V, et al. Loss of meal-induced decrease in plasma ghrelin levels in patients with anorexia nervosa. J Clin Endocrinol Metab 2003; 88:1678-1682.
24. •] of a regulation of ghrelin release by vagal stimulation. Ghrelin was suppressed further by a combination of modified followed by oral fat ingestion compared with fat ingestion only. The study also suggests that ghrelin regulation is independent of glucose and insulin concentrations because these remained low or static, respectively.
25. Vallejo-Cremades MT, Gomez-Garcia L, Chacatas-Cortesao M, et al. Enriched protein diet-modified ghrelin expression and secretion in rats. Regul Pept 2004; 121:113-119. In this study, the effect of four diets differing in macronutrient composition were tested on ghrelin levels and gut morphology and proliferation. Rats fed on high-protein diets for 7 days had the highest fasting ghrelin levels as well as higher duodenal crypt and villous length compared with the other diets. This was confirmed by higher ghrelin mRNA expression in the gastric fundus.
26. Calissendorff J, Danielsson O, Brismar K, Rojdmark S. Inhibitory effect of alcohol on ghrelin secretion in normal man. Eur J Endocrinol 2005; 152:743-747.
27. Lugari R, Dell'Anna C, Ugolotti D, et al. Effect of nutrient ingestion on glucagon-like peptide 1 (7-36) amide secretion in human type 1 and type 2 diabetes. Horm Metab Res 2000; 32:424-428.
28. Vilsboll T, Krarup T, Sonne J, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88:2706-2713.
29. Elliott RM, Morgan LM, Tredger JA, et al. Glucagon-like peptide-1 (7-36) amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. J Endocrinol 1993; 138:159-166.
30. Herrmann C, Goke R, Richter G, et al. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion 1995; 56:117-126.
31. Brynes AE, Edwards CMB, Ghatei MA, et al. A randomised four-intervention crossover study investigating the effect of carbohydrates on daytime profiles of insulin, glucose, non-esterified fatty acids and triacylglycerides in middle aged men. Br J Nutr 2003; 89:207-218.
32. Brynes AE, Frost GS, Edwards CM, et al. Plasma glucagon-like peptide-1 (7-36) amide (GLP-1) response to liquid phase, solid phase, and meals of differing lipid composition. Nutrition 1998; 14:433-436.
33. Murphy MC, Chapman C, Lovegrove JA, et al. Meal frequency; does it determine postprandial lipaemia? Eur J Clin Nutr 1996; 50:491-497.
34. Feinle C, Chapman IM, Wishart J, Horowitz M. Plasma glucagon-like peptide-1 (GLP-1) responses to duodenal fat and glucose infusions in lean and obese men. Peptides 2002; 23:1491-1495.
35. Lavin JH, Wittert GA, Andrews J, et al. Interaction of insulin, glucagon-like peptide 1, gastric inhibitory polypeptide, and appetite in response to intraduodenal carbohydrate. Am J Clin Nutr 1998; 68:591-598.
36. Lavin JH, Wittert G, Sun WM, et al. Appetite regulation by carbohydrate: role of blood glucose and gastrointestinal hormones. Am J Physiol 1996; 271:E209-E214.
37. Balks HJ, Holst JJ, von zur Muhlen A, Brabant G. Rapid oscillations in plasma glucagon-like peptide-1 (GLP-1) in humans: cholinergic control of GLP-1 secretion via muscarinic receptors. J Clin Endocrinol Metab 1997; 82:786-790.
38. O'Donovan DG, Doran S, Feinle-Bisset C, et al. Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes. J Clin Endocrinol Metab 2004; 89:3431-3435. This article highlights the importance of the rate of small intestinal glucose delivery on blood glucose, insulin and GLP-1 in eight healthy individuals and eight with type 2 diabetes. A variable infusion rate resulted in a larger GLP-1 response than a constant rate over the first 30 min.
39. Kong MF, Chapman I, Goble E, et al. Effects of oral fructose and glucose on plasma GLP-1 and appetite in normal subjects. Peptides 1999; 20:545-551.
40. Rayner CK, Park HS, Wishart JM, et al. Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans. Am J Physiol Regul Integr Comp Physiol 2000; 278:R360-R366.
41. Juntunen KS, Niskanen LK, Liukkonen KH, et al. Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects. Am J Clin Nutr 2002; 75:254-262.
42. Juntunen KS, Laaksonen DE, Autio K, et al. Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread. Am J Clin Nutr 2003; 78:957-964.
43. Reimer RA, McBurney MI. Dietary fiber modulates intestinal proglucagon messenger ribonucleic acid and postprandial secretion of glucagon-like peptide-1 and insulin in rats. Endocrinology 1996; 137:3948-3956.
44. Massimino SP, McBurney MI, Field CJ, et al. Fermentable dietary fiber increases GLP-1 secretion and improves glucose homeostasis despite increased intestinal glucose transport capacity in healthy dogs. J Nutr 1998; 128:1786-1793.
45. Frost GS, Brynes AE, Dhillo WS, et al. The effects of fiber enrichment of pasta and fat content on gastric emptying, GLP-1, glucose, and insulin responses to a meal. Eur J Clin Nutr 2003; 57:293-298.
46. Boyd KA, O'Donovan DG, Doran S, et al. High-fat diet effects on gut motility, hormone, and appetite responses to duodenal lipid in healthy men. Am J Physiol Gastrointest Liver Physiol 2003; 284:G188-G196.
47. Feltrin KL, Little TJ, Meyer JH, et al. Effects of intraduodenal fatty acids on appetite, antropyloroduodenal motility, and plasma CCK and GLP-1 in humans vary with their chain length. Am J Physiol Regul lntegr Comp Physiol 2004; 287:R524-R533. Eight healthy individuals participated in this double-blind randomized trial to elucidate whether GLP-1 release is dependent on fatty acid chain length. The intraduodenal infusion of lauric (C12) acid at 0.375 kcal/min stimulated GLP-1 release, whereas deconoic (C10) acid did not.
48. Hirasawa A, Tsumaya K, Awaji T, et al. Free fatty acids regulate gut incretin glucagon-like peptide-1 secretion through GPR120. Nat Med 2005; 11:90-94. This article adds to previous work on fatty acid stimulation of GLP-1 with a more mechanistic perspective. The authors show that stimulation of the G-protein-coupled receptor for unsaturated fatty acids, GPR120, promotes the in-vivo and invitro secretion of GLP-1 and causes insulin release.
49. Beysen C, Karpe F, Fielding BA, et al. Interaction between specific fatty acids, GLP-1 and insulin secretion in humans. Diabetologia 2002; 45:1533-1541.
50. Brynes AE, Edwards CM, Jadhav A, et al. Diet-induced change in fatty acid composition of plasma triacylglycerols is not associated with change in glucagon-like peptide 1 or insulin sensitivity in people with type 2 diabetes. Am J Clin Nutr 2000; 72:1111-1118.
51. O'Donovan D, Horowitz M, Russo A, et al. Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes. Diabetologia 2004; 47:2208-2214. O'Donovan's group assesses how the acute administration of the lipase inhibitor, orlistat, influences the GLP-1 response to a high-fat/carbohydrate meal (58% fat) in eight type 2 diabetic patients. Orlistat (120 mg) caused a more rapid rate of gastric emptying, but a lower GLP-1 response between 60 and 180 min post-prandially.
52. Pilichiewicz A, O'Donovan D, Feinle C, et al. Effect of lipase inhibition on gastric emptying of, and the glycemic and incretin responses to, an oil/aqueous drink in type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88:3829-3834.
53. Feinle C, O'Donovan D, Doran S, et al. Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans. Am J Physiol Gastrointest Liver Physiol 2003; 284:G798-G807.
54. Damci T, Yalin S, Balci H, et al. Orlistat augments postprandial increases in glucagon-like peptide 1 in obese type 2 diabetic patients. Diabetes Care 2004; 27:1077-1080. This article contradicts O'Donovan's work; here the administration of 120 mg orlistat alongside a standard meal (38% fat) resulted in a significantly enhanced GLP-1 response in 29 type 2 diabetic patients.
55. Katsuma S, Hirasawa A, Tsujimoto G. Bile acids promote glucagon-like peptide-1 secretion through TGR5 in a murine enteroendocrine cell line STC-1. Biochem Biophys Res Commun 2005; 329:386-390.
56. Nilsson M, Stenberg M, Frid AH, et al. Glycemia and insulinemia in healthy subjects after lactose-equivalent meals of milk and other food proteins: the role of plasma amino acids and incretins. Am J Clin Nutr 2004; 80:1246-1253.
57. Sanggaard KM, Holst JJ, Rehfeld JF, et al. Different effects of whole milk and a fermented milk with the same fat and lactose content on gastric emptying and postprandial lipaemia, but not on glycaemic response and appetite. Br J Nutr 2004; 92:447-459.
58. Hall WL, Millward DJ, Long SJ, Morgan LM. Casein and whey exert different effects on plasma amino acid profiles, gastrointestinal hormone secretion and appetite. Br J Nutr 2003; 89:239-248.
59. Calbet JA, Holst JJ. Gastric emptying, gastric secretion and enterogastrone response after administration of milk proteins or their peptide hydrolysates in humans. Eur J Nutr 2004; 43:127-139. This small study investigates the effect of protein fractionation on gastric emptying and incretin release. The GLP-1 response to the ingestion of cows' milk protein is not dependent on protein fractionation, small differences in amino acid composition or protein solubility.
60. Johnston KL, Clifford MN, Morgan LM. Coffee acutely modifies gastrointestinal hormone secretion and glucose tolerance in humans: glycemic effects of chlorogenic acid and caffeine. Am J Clin Nutr 2003; 78:728-733.
61. McCarty MF. A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Med Hypotheses 2005; 64:848-853. A thorough discussion of possible mechanisms by which coffee may reduce the risk of diabetes, including Johnston's observation of increased GLP-1 release, which has been attributed to the chlorogenic acid-induced inhibition of glucose absorption.
62. Onaga T, Zabielski R, Kato S. Multiple regulation of peptide YY secretion in the digestive tract. Peptides 2002; 23:279-290.
63. Pedersen-Bjergaard U, Host U, Kelbaek H, et al. Influence of meal composition on postprandial peripheral plasma concentrations of vasoactive peptides in man. Scand J Clin Lab Invest 1996; 56:497-503.
64. Adrian TE, Ferri GL, Bacarese-Hamilton AJ, et al. Human distribution and release of a putative new gut hormone, peptide YY. Gastroenterology 1985; 89:1070-1077.
65. Greeley GH Jr, Hashimoto T, Izukura M, et al. A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. Endocrinology 1989; 125:1761-1765.
66. Pironi L, Stanghellini V, Miglioli M, et al. Fat-induced ileal brake in humans: a dose-dependent phenomenon correlated to the plasma levels of peptide YY. Gastroenterology 1993; 105:733-739.
67. Plaisancie P, Dumoulin V, Chayvialle JA, Cuber JC. Luminal peptide YY-releasing factors in the isolated vascularly perfused rat colon. J Endocrinol 1996; 151:421-429.
68. Serrano P, Yago MD, Manas M, et al. Influence of type of dietary fat (olive and sunflower oil) upon gastric acid secretion and release of gastrin, somatostatin, and peptide YY in man. Dig Dis Sci 1997; 42:626-633.
69. Adrian TE, Savage AP, Sagor GR, et al. Effect of peptide YY on gastric, pancreatic, and biliary function in humans. Gastroenterology 1985; 89:494-499.
70. Adrian TE, Ballantyne GH, Longo WE, et al. Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon. Gut 1993; 34:1219-1224.
71. Stanley S, Wynne K, Bloom S. Gastrointestinal satiety signals III. Glucagon-like peptide 1, oxyntomodulin, peptide YY, and pancreatic polypeptide. Am J Physiol Gastrointest Liver Physiol 2004; 286:G693-G697.
72. Liddle RA, Goldfine ID, Rosen MS, et al. Cholecystokinin bioactivity in human plasma. Molecular forms, responses to feeding, and relationship to gallbladder contraction. J Clin Invest 1985; 75:1144-1152.
73. Liddle RA. Cholecystokinin. In: Walsh JH, Dockray GJ, editors. Gut peptides: biochemistry and physiology. New York: Raven; 1994. pp. 175-216.
74. Himeno S, Tarui S, Kanayama S, et al. Plasma cholecystokinin responses after ingestion of liquid meal and intraduodenal infusion of fat, amino acids, or hydrochloric acid in man: analysis with region specific radioimmunoassay. Am J Gastroenterol 1983; 78:703-707.
75. Hopman WP, Jansen JB, Lamers CB. Comparative study of the effects of equal amounts of fat, protein, and starch on plasma cholecystokinin in man. Scand J Gastroenterol 1985; 20:843-847.
76. Froehlich F, Gonvers JJ, Fried M. Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man. Dig Dis Sci 1995; 40:529-533.
77. Schwizer W, Asal K, Kreiss C, et al. Roleof lipase in the regulation of upper gastrointestinal function in humans. Am J Physiol 1997; 273:G612-G620.
78. Hildebrand P, Petrig C, Burckhardt B, et al. Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release. Gastroenterology 1998; 114:123-129.
79. Feinle C, Rades T, Otto B, Fried M. Fat digestion modulates gastrointestinal sensations induced by gastric distension and duodenal lipid in humans. Gastroenterology 2001; 120:1100-1107.
80. McLaughlin J, Grazia LM, Jones MN, et al. Fatty acid chain length determines cholecystokinin secretion and effect on human gastric motility. Gastroenterology 1999; 116:46-53.
81. Isaacs PE, Ladas S, Forgacs IC, et al. Comparison of effects of ingested medium- and long-chain triglyceride on gallbladder volume and release of cholecystokinin and other gut peptides. Dig Dis Sci 1987; 32:481-486.
82. Symersky T, Vu MK, Frolich M, et al. The effect of equicaloric medium-chain and long-chain triglycerides on pancreas enzyme secretion. Clin Physiol Funct Imaging 2002; 22:307-311.
83. Beardshall K, Frost G, Morarji Y, et al. Saturation of fat and cholecystokinin release: implications for pancreatic carcinogenesis. Lancet 1989; 2:1008-1010.
84. McLaughlin JT, Lomax RB, Hall L, et al. Fatty acids stimulate cholecystokinin secretion via an acyl chain length-specific, Ca2+-dependent mechanism in the enteroendocrine cell line STC-1. J Physiol 1998; 513:11-18.
85. Brand SJ, Morgan RG. The release of rat intestinal cholecystokinin after oral trypsin inhibitor measured by bio-assay. J Physiol 1981; 319:325-343.
86. Calam J, Bojarski JC, Springer CJ. Raw soya-bean flour increases cholecystokinin release in man. Br J Nutr 1987; 58:175-179.
87. Nishi T, Hara H, Hira T, Tomita F. Dietary protein peptic hydrolysates stimulate cholecystokinin release via direct sensing by rat intestinal mucosal cells. Exp Biol Med (Maywood) 2001; 226:1031-1036.
88. Pasman WJ, Blokdijk VM, Bertina FM, et al. Effect of two breakfasts, different in carbohydrate composition, on hunger and satiety and mood in healthy men. Int J Obes Relat Metab Disord 2003; 27:663-668.
89. Douglas BR, Jansen JB, Tham RT, Lamers CB. Coffee stimulation of cholecystokinin release and gallbladder contraction in humans. Am J Clin Nutr 1990; 52:553-556.
90. Heini AF, Lara-Castro C, Schneider H, et al. Effect of hydrolyzed guar fiber on fasting and postprandial satiety and satiety hormones: a double-blind, placebo-controlled trial during controlled weight loss. Int J Obes Relat Metab Disord 1998; 22:906-909.
91. Bourdon I, Olson B, Backus R, et al. Beans, as a source of dietary fiber, increase cholecystokinin and apolipoprotein b48 response to test meals in men. J Nutr 2001; 131:1485-1490.