Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPARα and FGF21 transcripts in vivo

American Journal of Physiology - Endocrinology and Metabolism

Volumn 299, Issue 4, 2010, Pages

  Berglund, Eric D ^a   Kang, Li ^a   Lee Young, Robert S ^a   Hasenour, Clinton M ^a   Lustig, Daniel G ^a   Lynes, Sara E ^a   Donahue, E Patrick ^a   Swift, Larry L ^a   Charron, Maureen J ^b   Wasserman, David H ^a,c  

^a VANDERBILT UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^c NATIONAL INSTITUTES OF HEALTH   (United States)

Author keywords

Adenosine 5 monophosphate activated protein kinase; Fibroblast growth factor 21; Peroxisome proliferator activated receptor

Indexed keywords

ACETYL COENZYME A CARBOXYLASE; ADENOSINE MONOPHOSPHATE ACTIVATED PROTEIN KINASE ALPHA; ADENOSINE TRIPHOSPHATE; ADENYLATE KINASE; FIBROBLAST GROWTH FACTOR 21; GLUCAGON; GLUCAGON RECEPTOR; LIPID; MESSENGER RNA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; THREONINE; UNCLASSIFIED DRUG; CATECHOLAMINE; FATTY ACID; FIBROBLAST GROWTH FACTOR; GLUCOSE BLOOD LEVEL; INSULIN; LIPID EMULSION;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; DIET RESTRICTION; ENZYME PHOSPHORYLATION; EXERCISE; FEMALE; HYPERLIPIDEMIA; IN VIVO STUDY; LIPID METABOLISM; LIVER; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; REGULATORY MECHANISM; WILD TYPE; ANIMAL; AREA UNDER THE CURVE; BIOSYNTHESIS; BLOOD; C57BL MOUSE; ENZYMOLOGY; GENETICS; GLUCOSE BLOOD LEVEL; GLUCOSE CLAMP TECHNIQUE; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION;

ADENYLATE KINASE; ANIMALS; AREA UNDER CURVE; BLOOD GLUCOSE; CATECHOLAMINES; FAT EMULSIONS, INTRAVENOUS; FATTY ACIDS, NONESTERIFIED; FEMALE; FIBROBLAST GROWTH FACTORS; GLUCAGON; GLUCOSE CLAMP TECHNIQUE; INSULIN; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; PHYSICAL CONDITIONING, ANIMAL; PPAR ALPHA; RECEPTORS, GLUCAGON; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA, MESSENGER; SIGNAL TRANSDUCTION;

EID: 77957556136     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00263.2010     Document Type: Article

References (51)

1. Anavi S, Ilan E, Tirosh O, Madar Z. Infusion of a lipid emulsion modulates AMPK and related proteins in rat liver, muscle, and adipose tissues. Obesity (Silver Spring) 18: 1108-1115, 2010.
2. Ayala JE, Bracy DP, McGuinness OP, Wasserman DH. Considerations in the design of hyperinsulinemic-euglycemic clamps in the conscious mouse. Diabetes 55: 390-397, 2006.
3. Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab 5: 426-437, 2007. (Pubitemid 46825495)
4. Basu A, Shah P, Nielsen M, Basu R, Rizza RA. Effects of type 2 diabetes on the regulation of hepatic glucose metabolism. J Investig Med 52: 366-374, 2004. (Pubitemid 39552605)
5. Basu R, Schwenk WF, Rizza RA. Both fasting glucose production and disappearance are abnormal in people with "mild" and "severe" type 2 diabetes. Am J Physiol Endocrinol Metab 287: E55-E62, 2004.
6. Berglund ED, Lee-Young RS, Lustig DG, Lynes SE, Donahue EP, Camacho RC, Meredith ME, Magnuson MA, Charron MJ, Wasserman DH. Hepatic energy state is regulated by glucagon receptor signaling in mice. J Clin Invest 119: 2412-2422, 2009.
7. Berglund ED, Li CY, Bina HA, Lynes SE, Michael MD, Shanafelt AB, Kharitonenkov A, Wasserman DH. Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology 150: 4084-4093, 2009.
8. Berglund ED, Li CY, Poffenberger G, Ayala JE, Fueger PT, Willis SE, Jewell MM, Powers AC, Wasserman DH. Glucose metabolism in vivo in four commonly used inbred mouse strains. Diabetes 57: 1790-1799, 2008.
9. Bunger M, van den Bosch HM, van der Meijde J, Kersten S, Hooiveld GJ, Muller M. Genome-wide analysis of PPARalpha activation in murine small intestine. Physiol Genomics 30: 192-204, 2007.
10. Camacho RC, Donahue EP, James FD, Berglund ED, Wasserman DH. Energy state of the liver during short-term and exhaustive exercise in C57BL/6J mice. Am J Physiol Endocrinol Metab 290: E405-E408, 2006.
11. Carlson CL, Winder WW. Liver AMP-activated protein kinase and acetyl-CoA carboxylase during and after exercise. J Appl Physiol 86: 669-674, 1999.
12. Chan TM, Exton JH. A rapid method for the determination of glycogen content and radioactivity in small quantities of tissue or isolated hepatocytes. Anal Biochem 71: 96-105, 1976.
13. Chen WW, Li L, Yang GY, Li K, Qi XY, Zhu W, Tang Y, Liu H, Boden G. Circulating FGF-21 levels in normal subjects and in newly diagnose patients with Type 2 diabetes mellitus. Exp Clin Endocrinol Diabetes 116: 65-68, 2008.
14. Dzamko N, Schertzer JD, Ryall JG, Steel R, Macaulay SL, Wee S, Chen ZP, Michell BJ, Oakhill JS, Watt MJ, Jorgensen SB, Lynch GS, Kemp BE, Steinberg GR. AMPK-independent pathways regulate skeletal muscle fatty acid oxidation. J Physiol 586: 5819-5831, 2008.
15. Forman BM, Chen J, Evans RM. The peroxisome proliferator-activated receptors: ligands and activators. Ann NY Acad Sci 804: 266-275, 1996. (Pubitemid 27056615)
16. Fryer LG, Parbu-Patel A, Carling D. The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277: 25226-25232, 2002. (Pubitemid 34951829)
17. Fueger PT, Li CY, Ayala JE, Shearer J, Bracy DP, Charron MJ, Rottman JN, Wasserman DH. Glucose kinetics and exercise tolerance in mice lacking the GLUT4 glucose transporter. J Physiol 582: 801-812, 2007.
18. Galbo H, Holst JJ, Christensen NJ. Glucagon and plasma catecholamine responses to graded and prolonged exercise in man. J Appl Physiol 38: 70-76, 1975.
19. Gelling RW, Du XQ, Dichmann DS, Romer J, Huang H, Cui L, Obici S, Tang B, Holst JJ, Fledelius C, Johansen PB, Rossetti L, Jelicks LA, Serup P, Nishimura E, Charron MJ. Lower blood glucose, hyperglucagonemia, and pancreatic alpha cell hyperplasia in glucagon receptor knockout mice. Proc Natl Acad Sci USA 100: 1438-1443, 2003.
20. Gomez-Valades AG, Mendez-Lucas A, Vidal-Alabro A, Blasco FX, Chillon M, Bartrons R, Bermudez J, Perales JC. Pck1 gene silencing in the liver improves glycemia control, insulin sensitivity, and dyslipidemia in db/db mice. Diabetes 57: 2199-2210, 2008.
21. Griffiths MA, Fiebig R, Gore MT, Baker DH, Esser K, Oscai L, Ji LL. Exercise down-regulates hepatic lipogenic enzymes in food-deprived and refed rats. J Nutr 126: 1959-1971, 1996.
22. Hawley SA, Gadalla AE, Olsen GS, Hardie DG. The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51: 2420-2425, 2002.
23. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammadi M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA. Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Cell Metab 5: 415-425, 2007.
24. Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 284: E671-E678, 2003.
25. Kharitonenkov A, Shanafelt AB. Fibroblast growth factor-21 as a therapeutic agent for metabolic diseases. BioDrugs 22: 37-44, 2008. (Pubitemid 351158533)
26. Kimball SR, Siegfried BA, Jefferson LS. Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 279: 54103-54109, 2004.
27. Krishna MG, Coker RH, Lacy DB, Zinker BA, Halseth AE, Wasserman DH. Glucagon response to exercise is critical for accelerated hepatic glutamine metabolism and nitrogen disposal. Am J Physiol Endocrinol Metab 279: E638-E645, 2000.
28. Lavoie JM, Bergeron R, Latour MG. Regulatory impact of intra-hepatic carbohydrate and lipid metabolism. Can J Appl Physiol 30: 282-291, 2005. (Pubitemid 40880708)
29. Longuet C, Sinclair EM, Maida A, Baggio LL, Maziarz M, Charron MJ, Drucker DJ. The glucagon receptor is required for the adaptive metabolic response to fasting. Cell Metab 8: 359-371, 2008.
30. Lundasen T, Hunt MC, Nilsson LM, Sanyal S, Angelin B, Alexson SE, Rudling M. PPARalpha is a key regulator of hepatic FGF21. Biochem Biophys Res Commun 360: 437-440, 2007.
31. Macdonald IA, Lake DM. An improved technique for extracting catecholamines from body fluids. J Neurosci Methods 13: 239-248, 1985.
32. Marliss EB, Aoki TT, Unger RH, Soeldner JS, Cahill GF Jr. Glucagon levels and metabolic effects in fasting man. J Clin Invest 49: 2256-2270, 1970.
33. Morgan CR, Lazarow A. Immunoassay of insulin using a two-antibody system. Proc Soc Exp Biol Med 110: 29-32, 1962.
34. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, Mihaylova MM, Nelson MC, Zou Y, Juguilon H, Kang H, Shaw RJ, Evans RM. AMPK and PPARdelta agonists are exercise mimetics. Cell 134: 405-415, 2008.
35. Sindelar DK, Chu CA, Rohlie M, Neal DW, Swift LL, Cherrington AD. The role of fatty acids in mediating the effects of peripheral insulin on hepatic glucose production in the conscious dog. Diabetes 46: 187-196, 1997.
36. Suchankova G, Tekle M, Saha AK, Ruderman NB, Clarke SD, Gettys TW. Dietary polyunsaturated fatty acids enhance hepatic AMP-activated protein kinase activity in rats. Biochem Biophys Res Commun 326: 851-858, 2005. (Pubitemid 39655997)
37. Svedberg J, Stromblad G, Wirth A, Smith U, Bjorntorp P. Fatty acids in the portal vein of the rat regulate hepatic insulin clearance. J Clin Invest 88: 2054-2058, 1991.
38. Uebanso T, Taketani Y, Fukaya M, Sato K, Takei Y, Sato T, Sawada N, Amo K, Harada N, Arai H, Yamamoto H, Takeda E. Hypocaloric high-protein diet improves fatty liver and hypertriglyceridemia in sucrose-fed obese rats via two pathways. Am J Physiol Endocrinol Metab 297: E76-E84, 2009.
39. Unger RH, Eisentraut AM, Madison LL. The effects of total starvation upon the levels of circulating glucagon and insulin in man. J Clin Invest 42: 1031-1039, 1963.
40. van Raalte DH, Li M, Pritchard PH, Wasan KM. Peroxisome proliferator- activated receptor (PPAR)-alpha: a pharmacological target with a promising future. Pharm Res 21: 1531-1538, 2004. (Pubitemid 41184380)
41. Wasserman DH. Four grams of glucose. Am J Physiol Endocrinol Metab 296: E11-E21, 2009.
42. Wasserman DH. Regulation of glucose fluxes during exercise in the postabsorptive state. Annu Rev Physiol 57: 191-218, 1995.
43. Wasserman DH, Lickley HL, Vranic M. Interactions between glucagon and other counterregulatory hormones during normoglycemic and hypoglycemic exercise in dogs. J Clin Invest 74: 1404-1413, 1984. (Pubitemid 15200233)
44. Wasserman DH, Spalding JA, Lacy DB, Colburn CA, Goldstein RE, Cherrington AD. Glucagon is a primary controller of hepatic glycogenolysis and gluconeogenesis during muscular work. Am J Physiol Endocrinol Metab 257: E108-E117, 1989.
45. Williams EL, Rodriguez SM, Beitz DC, Donkin SS. Effects of short-term glucagon administration on gluconeogenic enzymes in the liver of midlactation dairy cows. J Dairy Sci 89: 693-703, 2006.
46. Winder WW, Hickson RC, Hagberg JM, Ehsani AA, McLane JA. Training-induced changes in hormonal and metabolic responses to submaximal exercise. J Appl Physiol 46: 766-771, 1979.
47. Witters LA, Gao G, Kemp BE, Quistorff B. Hepatic 5′-AMP-activated protein kinase: zonal distribution and relationship to acetyl-CoA carboxylase activity in varying nutritional states. Arch Biochem Biophys 308: 413-419, 1994. (Pubitemid 124007826)
48. Wojtaszewski JF, Mourtzakis M, Hillig T, Saltin B, Pilegaard H. Dissociation of AMPK activity and ACCbeta phosphorylation in human muscle during prolonged exercise. Biochem Biophys Res Commun 298: 309-316, 2002. (Pubitemid 35333706)
49. Wu Y, Song P, Xu J, Zhang M, Zou MH. Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase. J Biol Chem 282: 9777-9788, 2007.
50. Za'tara G, Bar-Tana J, Kalderon B, Suter M, Morad E, Samovski D, Neumann D, Hertz R. AMPK activation by long chain fatty acyl analogs. Biochem Pharmacol 76: 1263-1275, 2008.
51. Zhang X, Yeung DC, Karpisek M, Stejskal D, Zhou ZG, Liu F, Wong RL, Chow WS, Tso AW, Lam KS, Xu A. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes 57: 1246-1253, 2008.