Hepatic Akt Activation Induces Marked Hypoglycemia, Hepatomegaly, and Hypertriglyceridemia with Sterol Regulatory Element Binding Protein Involvement

Diabetes

Volumn 52, Issue 12, 2003, Pages 2905-2913

  Ono, Hiraku ^a   Shimano, Hitoshi ^b   Katagiri, Rideki ^c   Yahagi, Naoya ^d   Sakoda, Hideyuki ^a   Onishi, Yukiko ^a   Anai, Motonobu ^a   Ogihara, Takehide ^c   Fujishiro, Midori ^d   Viana, Amelia Y I ^e   Fukushima, Yasushi ^d   Abe, Miho ^d   Shojima, Nobuhiro ^d   Kikuchi, Masatoshi ^a   Yamada, Nobuhiro ^b   Oka, Yoshitomo ^c   Asano, Tomoichiro ^d,f  

^a INSTITUTE FOR ADULT DISEASES   (Japan)

^b UNIVERSITY OF TSUKUBA   (Japan)

^c TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^d UNIVERSITY OF TOKYO   (Japan)

^e NAGOYA UNIVERSITY   (Japan)

^f UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

6 PHOSPHOFRUCTOKINASE; ACETYL COENZYME A CARBOXYLASE; ACYL COENZYME A DESATURASE; BINDING PROTEIN; FATTY ACID SYNTHASE; GLUCOKINASE; GLUCOSE 6 PHOSPHATASE; GLUCOSE 6 PHOSPHATE DEHYDROGENASE; PROTEIN KINASE B; PROTEIN SUBUNIT; STEROL; STEROL REGULATORY ELEMENT BINDING PROTEIN; TRIACYLGLYCEROL;

ADENOVIRUS; ANIMAL MODEL; ARTICLE; BIOACCUMULATION; CONTROLLED STUDY; ENZYME ACTIVATION; FATTY ACID SYNTHESIS; FATTY LIVER; GENE OVEREXPRESSION; HEPATOMEGALY; HYPERTRIGLYCERIDEMIA; HYPOGLYCEMIA; KNOCKOUT MOUSE; MOUSE; MYRISTYLATION; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION;

ANIMALS; CCAAT-ENHANCER-BINDING PROTEINS; DNA-BINDING PROTEINS; ENZYMES; FATTY LIVER; GLUCONEOGENESIS; GLYCOLYSIS; HEPATOMEGALY; HUMANS; HYPERTRIGLYCERIDEMIA; HYPOGLYCEMIA; LIPIDS; LIVER; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; MICE, TRANSGENIC; PHENOTYPE; PROTEIN-SERINE-THREONINE KINASES; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RNA, MESSENGER; STEROL REGULATORY ELEMENT BINDING PROTEIN 1; TRANSCRIPTION FACTORS;

EID: 10744228468     PISSN: 00121797     EISSN: None     Source Type: Journal    
DOI: 10.2337/diabetes.52.12.2905     Document Type: Article

References (52)

1. Saltiel AR, Kahn CR: Insulin signalling and the regulation of glucose and lipid metabolism. Nature 414:799-806, 2001
2. Whiteman EL, Cho H, Birnbaum MJ: Role of Akt/protein kinase B in metabolism. Trends Endocrinol Metab 13:444-451, 2002
3. Miyake K, Ogawa W, Matsumoto M, Nakamura T, Sakaue H, Kasuga M: Hypermsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver. J Clin Invest 110:1483-1491, 2002
4. Czech MP, Corvera S: Signaling mechanisms that regulate glucose transport. J Biol Chem 274:1865-1868, 1999
5. Pessin JE, Saltiel AR: Signaling pathways in insulin action: molecular targets of insulin resistance. J Clin Invest 106:165-169, 2000
6. Calera MR, Martinez C, Liu H, Jack AK, Birnbaum MJ, Pilch PF: Insulin increases the association of Akt-2 with Glut4-containing vesicles. J Biol Chem 273:7201-7204, 1998
7. Kohn AD, Summers SA, Birnbaum MJ, Roth RA: Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation. J Biol Chem 271:31372-31378, 1996
8. Tanti JF, Grillo S, Gremeaux T, Coffer PJ, Van Obberghen E, Le Marchand-Brustel Y: Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes. Endocrinology 138:2005-2010, 1997
9. Hqjduch E, Alessi DR, Hemmings BA, Hundal HS: Constitutive activation of protein kinase B a by membrane targeting promotes glucose and system A amino acid transport, protein synthesis, and inactivation of glycogen synthase kinase 3 in L6 muscle cells. Diabetes 47:1006-1013, 1998
10. Cho H, Mu J, Kim JK, Thorvaldsen JL, Chu Q, Kaestner KH, Bartolomei MS, Shulman GI, Birnbaum MJ: Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB beta). Science 292:1728-1731, 2001
11. O'Brien RM, Granner DK: Regulation of gene expression by insulin. Physiol Rev 76:1109-1161, 1996
12. Chen D, Fucini RV, Olson AL, Hemmings BA, Pessin JE: Osmotic shock inhibits insulin signaling by maintaining Akt/protein kinase B in an inactive dephosphorylated state. Mol Cell Biol 19:4684-4694, 1999
13. Cross DA, Alessi DR, Cohen P, Andjelkovich M, Hemmings BA: Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B. Nature 378:785-789, 1995
14. van Weeren PC, de Bruyn KM, de Vries-Smits AM, van Lint J, Burgering BM: Essential role for protein kinase B (PKB) in insulin-induced glycogen synthase kinase 3 inactivation: characterization of dominant-negative mutant of PKB. J Biol Chem 273:13150-13156, 1998
15. Fleischmann M, Iynedjian PB: Regulation of sterol regulatory-element binding protein 1 gene expression in liver: role of insulin and protein kinase B/cAkt. Biochem J 349:13-17, 2000
16. Horton JD, Bashmakov Y, Shimomura I, Shimano H: Regulation of sterol regulatory element binding proteins in livers of fasted and refed mice. Proc Natl Acad Sci U S A 95:5987-5992, 1998
17. Osborne TF: Sterol regulatory element-binding proteins (SREBPs): key regulators of nutritional homeostasis and insulin action. J Biol Chem 275:32379-32382, 2000
18. Azzout-Marniche D, Becard D, Guichard C, Foretz M, Ferre P, Foufelle F: Insulin effects on sterol regulatory-element-binding protein-1c (SREBP-1c) transcriptional activity in rat hepatocytes. Biochem J 350:389-393, 2000
19. Becard D, Hainault I, Azzout-Marniche D, Bertry-Coussot L, Ferre P, Foufelle F: Adenovirus-mediated overexpression of sterol regulatory element binding protein-1c mimics insulin effects on hepatic gene expression and glucose homeostasis in diabetic mice. Diabetes 50:2425-2430, 2001
20. Foretz M, Pacot C, Dugail I, Lemarchand P, Guichard C, Le Liepvre X, Berthelier-Lubrano C, Spiegelman B, Kim JB, Ferre P, Foufelle F: ADD1/SREBP-1c is required in the activation of hepatic lipogenic gene expression by glucose. Mol Cell Biol 19:3760-3768, 1999
21. Foretz M, Guichard C, Ferre P, Foufelle F: Sterol regulatory element binding protein-1c is a major mediator of insulin action on the hepatic expression of glucokinase and lipogenesis-related genes. Proc Natl Acad Sci U S A 96:12737-12742, 1999
22. Chakravarty K, Leahy P, Becard D, Hakimi P, Foretz M, Ferre P, Foufelle F, Hanson RW: Sterol regulatory element-binding protein-1c mimics the negative effect of insulin on phosphoenolpyruvate carboxykinase (GTP) gene transcription. J Biol Chem 276:34816-34823, 2001
23. Shimomura I, Shimano H, Korn BS, Bashmakov Y, Horton JD: Nuclear sterol regulatory element-binding proteins activate genes responsible for the entire program of unsaturated fatty acid biosynthesis in transgenic mouse liver. J Biol Chem 273:35299-35306, 1998
24. Shimano H, Horton JD, Hammer RE, Shimomura I, Brown MS, Goldstein JL: Overproduction of cholesterol and fatty acids causes massive liver enlargement in transgenic mice expressing truncated SREBP-1a. J Clin Invest 98:1575-1584, 1996
25. Yamada T, Katagiri H, Asano T, Inukai K, Tsuru M, Kodama T, Kikuchi M, Oka Y: 3-phosphoinositide-dependent protein kinase 1, an Akt1 kinase, is involved in dephosphorylation of Thr-308 of Akt1 in Chinese hamster ovary cells. J Biol Chem 276:5339-5345, 2001
26. Ono H, Katagiri H, Funaki M, Anai M, Inukai K, Fukushima Y, Sakoda H, Ogihara T, Onishi Y, Fujishiro M, Kikuchi M, Oka Y, Asano T: Regulation of phosphoinositide metabolism, Akt phosphorylation, and glucose transport by PTEN (phosphatase and tensin homolog deleted on chromosome 10) in 3T3-L1 adipocytes. Mol Endocrinol 15:1411-1422, 2001
27. Sakoda H, Ogihara T, Anai M, Funaki M, Inukai K, Katagiri H, Fukushima Y, Onishi Y, Ono H, Fujishiro M, Kikuchi M, Oka Y, Asano T: Dexamethasone-induced insulin resistance in 3T3-L1 adipocytes is due to inhibition of glucose transport rather than insulin signal transduction. Diabetes 49: 1700-1708, 2000
28. Shimano H, Shimomura I, Hammer RE, Herz J, Goldstein JL, Brown MS, Horton JD: Elevated levels of SREBP-2 and cholesterol synthesis in livers of mice homozygous for a targeted disruption of the SREBP-1 gene. J Clin Invest 100:2115-2124, 1997
29. Bucolo G, David H: Quantitative determination of serum triglycerides by the use of enzymes. Clin Chem 19:476-482, 1973
30. Allain CC, Poon LS, Chan CS, Richmond W, Fu PC: Enzymatic determination of total serum cholesterol. Clin Chem 20:470-475, 1974
31. Folch J, Lees M, Stanley GHS: A simple method for the isolation and purification of total lipids from animal tissues. J Biol Chem 226:497-509, 1957
32. Bergmeyer HU, Bergmeyer J, Grassl M: Methods of Enzymatic Analysis. 3rd ed. Hoboken, NJ, Wiley, 1984, p. 11-18
33. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS: Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 99:838-845, 1997
34. Sheng Z, Otani H, Brown MS, Goldstein JL: Independent regulation of sterol regulatory element-binding proteins 1 and 2 in hamster liver. Proc Natl Acad Sci U S A 92:935-938, 1995
35. Shimomura I, Bashmakov Y, Ikemoto S, Horton JD, Brown MS, Goldstein JL: Insulin selectively increases SREBP-1c mRNA in the livers of rats with streptozotocin-induced diabetes. Proc Natl Acad Sci U S A 96:13656-13661, 1999
36. Kim JB, Sarraf P, Wright M, Yao KM, Mueller E, Solanes G, Lowell BB, Spiegelman BM: Nutritional and insulin regulation of fatty acid synthetase and leptin gene expression through ADD1/SREBP1. J Clin Invest 101:1-9, 1998
37. Kim JB, Spiegelman BM: ADD1/SREBP1 promotes adipocyte differentiation and gene expression linked to fatty acid metabolism. Genes Dev 10:1096-1107, 1996
38. Shimano H, Horton JD, Shimomura I, Hammer RE, Brown MS, Goldstein JL: Isoform 1c of sterol regulatory element binding protein is less active than isoform 1a in livers of transgenic mice and in cultured cells. J Clin Invest 99:846-854, 1997
39. Condorelli G, Drusco A, Stassi G, Bellacosa A, Roncarati R, Iaccarino G, Russo MA, Gu Y, Dalton N, Chung C, Latronico MV, Napoli C, Sadoshima J, Croce CM, Ross J Jr: Akt induces enhanced myocardial contractility and cell size in vivo in transgenic mice. Proc Natl Acad Sci U S A 99:12333-12338, 2002
40. Matsui T, Li L, Wu JC, Cook SA, Nagoshi T, Picard MH, Liao R, Rosenzweig A: Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart. J Biol Chem 277:22896-22901, 2002
41. Shioi T, McMullen JR, Kang PM, Douglas PS, Obata T, Franke TF, Cantley LC, Izumo S: Akt/protein kinase B promotes organ growth in transgenic mice. Mol Cell Biol 22:2799-2809, 2002
42. Tuttle RL, Gill NS, Pugh W, Lee JP, Koeberlein B, Furth EE, Polonsky KS, Naji A, Birnbaum MJ: Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBalpha. Nat Med 7:1133-1137, 2001
43. Bernal-Mizrachi E, Wen W, Stahlhut S, Welling CM, Permutt MA: Islet beta cell expression of constitutively active Akt1/PKB alpha induces striking hypertrophy, hyperplasia, and hyperinsulinemia. J Clin Invest 108:1631-1638, 2001
44. O'Brien RM, Granner DK: Regulation of gene expression by insulin. Biochem J 278:609-619, 1991
45. Nakae J, Kitamura T, Silver DL, Accili D: The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108:1359-1367, 2001
46. Schmoll D, Walker KS, Alessi DR, Grempler R, Burchell A, Guo S, Walther R, Unterman TG: Regulation of glucose-6-phosphatase gene expression by protein kinase Balpha and the forkhead transcription factor FKHR: evidence for insulin response unit-dependent and -independent effects of insulin on promoter activity. J Biol Chem 275:36324-36333, 2000
47. Lochhead PA, Coghlan M, Rice SQ, Sutherland C: Inhibition of GSK-3 selectively reduces glucose-6-phosphatase and phosphatase and phosphoenolypyruvate carboxykinase gene expression. Diabetes 50:937-946, 2001
48. Brunet A, Bonni A, Zigmond MJ, Lin MZ, Juo P, Hu LS, Anderson MJ, Arden KC, Blenis J, Greenberg ME: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96:857-868, 1999
49. Kops GJ, de Ruiter ND, De Vries-Smits AM, Powell DR, Bos JL, Burgering BM: Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398:630-634, 1999
50. Doiron B, Cuif MH, Kahn A, Diaz-Guerra MJ: Respective roles of glucose, fructose, and insulin in the regulation of the liver-specific pyruvate kinase gene promoter. J Biol Chem 269:10213-10216, 1994
51. Lefrancois-Martinez AM, Diaz-Guerra MJ, Vallet V, Kahn A, Antoine B: Glucose-dependent regulation of the L-pyruvate kinase gene in a hepatoma cell line is independent of insulin and cyclic AMP. Faseb J 8:89-96, 1994
52. Decaux JF, Antoine B, Kahn A: Regulation of the expression of the L-type pyruvate kinase gene in adult rat hepatocytes in primary culture. J Biol Chem 264:11584-11590, 1989