Hyperglycemia induced changes in liver: In vivo and in vitro studies

Current Diabetes Reviews

Volumn 5, Issue 2, 2009, Pages 67-78

  Dey, Aparajita ^a   Chandrasekaran, Karthikeyan ^a  

^a ANNA UNIVERSITY   (India)

Author keywords

Animal models; Hepatocytes; HepG2; High glucose; Liver; Steatohepatitis

Indexed keywords

8 HYDROXYDEOXYGUANOSINE; ALPHA TOCOPHEROL; APIGENIN; APOLIPOPROTEIN B48; ASCORBIC ACID; CONNECTIVE TISSUE GROWTH FACTOR; ENDOTHELIAL NITRIC OXIDE SYNTHASE; FARNESOID X RECEPTOR; GLUCOSE 6 PHOSPHATASE; HEAT SHOCK PROTEIN 72; INDUCIBLE NITRIC OXIDE SYNTHASE; INSULIN; MELATONIN; METFORMIN; MITOGEN ACTIVATED PROTEIN KINASE P38; NITRIC OXIDE SYNTHASE INHIBITOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PHOSPHOENOLPYRUVATE CARBOXYKINASE (GTP); PIOGLITAZONE; POLYPHENOL DERIVATIVE; PRASTERONE; PROBUCOL; RESVERATROL; ROSIGLITAZONE; S 17834; SELENIUM; SUPEROXIDE DISMUTASE; THIOCTIC ACID; TRANSCRIPTION FACTOR FKHR; UNCLASSIFIED DRUG;

ANTIOXIDANT ACTIVITY; DIABETES MELLITUS; DRUG TARGETING; GLUCOSE INTOLERANCE; GLUCOSE METABOLISM; GLUCOSE TRANSPORT; GLYCEMIC CONTROL; HORMONE ACTION; HUMAN; HYPERGLYCEMIA; HYPERINSULINEMIA; IN VITRO STUDY; IN VIVO STUDY; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; INSULIN SENSITIVITY; LIPID METABOLISM; LIVER CIRRHOSIS; LIVER DISEASE; LIVER DYSFUNCTION; LIVER NECROSIS; METABOLIC SYNDROME X; MITOCHONDRIAL RESPIRATION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONALCOHOLIC FATTY LIVER; NONHUMAN; OBESITY; OXIDATIVE PHOSPHORYLATION; OXIDATIVE STRESS; PANCREAS ISLET DISEASE; PRIORITY JOURNAL; REVIEW; ADAPTATION; ANIMAL; CELL CULTURE; LIVER; METABOLISM;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; CELLS, CULTURED; DIABETES MELLITUS, TYPE 2; HUMANS; HYPERGLYCEMIA; LIVER; LIVER DISEASES;

EID: 68349104492     PISSN: 15733998     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339909788166864     Document Type: Review

References (102)

1. Goh SY, Cooper ME. Clinical review: The role of advanced glycation end products in progression and complications of diabetes. J Clin Endocrinol Metab 2008; 93: 1143-52.
2. Kaneto H, Katakami N, Kawamori D, et al. Involvement of oxidative stress in the pathogenesis of diabetes. Antioxid Redox Signal 2007; 9: 355-66.
3. Kaneto H, Matsuoka TA, Katakami N, et al. Oxidative stress and the JNK pathway are involved in the development of Type 1 and Type 2 diabetes. Curr Mol Med 2007; 7: 674-86.
4. Evans JL, Goldfine ID, Maddux BA, Grodsky GM. Oxidative stress and stress- activated signaling pathways: a unifying hypothesis of Type 2 diabetes. Endocrinol Rev 2002; 23: 599-622.
5. Swiecki C, Stojadinovic A, Anderson J, Zhao A, Dawson H, Shea-Donohue T. Effect of hyperglycemia and nitric oxide synthase inhibition on heat tolerance and induction of heat shock protein 72 kDa in vivo. Am Surg 2003; 69: 587-92.
6. Díaz-Flores M, Ibáñez-Hernández MA, Galván RE, et al. Glucose-6-phosphate dehydrogenase activity and NADPH/NADP+ ratio in liver and pancreas are dependent on the severity of hyperglycemia in rat. Life Sci 2006; 78: 2601-7.
7. Duran-Sandoval D, Mautino G, Martin G, et al. Glucose regulates the expression of the farnesoid X receptor in liver. Diabetes 2004; 53: 890-8.
8. Portero-Otín M, Pamplona R, Ruiz MC, Cabiscol E, Prat J, Bellmunt MJ. Diabetes induces impairment in the proteolytic activity against oxidized proteins and a heterogeneous effect in nonenzymatic protein modifications in the cytosol of rat liver and kidney. Diabetes 1999; 48: 2215-20.
9. Hemmings SJ, Pekush RD. The impact of Type I diabetes on rat liver gamma-glutamyltranspeptidase. Mol Cell Biochem 1994; 139: 131-40.
10. Ebara T, Conde K, Kako Y, et al. Delayed catabolism of apoB-48 lipoproteins due to decreased heparan sulfate proteoglycan production in diabetic mice. J Clin Invest 2000; 105: 1807-18.
11. Demozay D, Rocchi S, Mas JC, et al. Fatty aldehyde dehydrogenase: potential role in oxidative stress protection and regulation of its gene expression by insulin. J Biol Chem 2004; 279: 6261-70.
12. Efendic S, Karlander S, Vranic M. Mild type II diabetes markedly increases glucose cycling in the postabsorptive state and during glucose infusion irrespective of obesity. J Clin Invest 1988; 81: 1953-61.
13. Li Y, Méchin MC, van de Werve G. Diabetes affects similarly the catalytic subunit and putative glucose-6-phosphate translocase of glucose-6-phosphatase. J Biol Chem 1999; 274: 33866-68.
14. Jin L, Xue HY, Jin LJ, Li SY, Xu YP. Antioxidant and pancreas-protective effect of aucubin on rats with streptozotocin-induced diabetes. Eur J Pharmacol 2008; 582: 162-7.
15. Sadi G, Yilmaz O, Güray T. Effect of vitamin C and lipoic acid on streptozotocin-induced diabetes gene expression: mRNA and protein expressions of Cu-Zn SOD and catalase. Mol Cell Biochem 2008; 309: 109-16.
16. Dinçer Y, Telci A, Kayali R, Yilmaz IA, Cakatay U, Akçay T. Effect of alpha-lipoic acid on lipid peroxidation and anti-oxidant enzyme activities in diabetic rats. Clin Exp Pharmacol Physiol 2002; 29: 281-4.
17. Desco MC, Asensi M, Márquez R, et al. Xanthine oxidase is involved in free radical production in Type 1 diabetes: protection by allopurinol. Diabetes 2002; 51: 1118-24.
18. Madar Z, Kalet-Litman S, Stark AH. Inducible nitric oxide synthase activity and expression in liver and hepatocytes of diabetic rats. Pharmacology 2005; 73: 106-12.
19. Sudnikovich EJ, Maksimchik YZ, Zabrodskaya SV, et al. Melatonin attenuates metabolic disorders due to streptozotocin-induced diabetes in rats. Eur J Pharmacol 2007; 569: 180-7.
20. Andican G, Burçak G. Oxidative damage to nuclear DNA in streptozotocin- diabetic rat liver. Clin Exp Pharmacol Physiol 2005; 32: 663-6.
21. Hsieh RH, Lien LM, Lin SH, Chen CW, Cheng HJ, Cheng HH. Alleviation of oxidative damage in multiple tissues in rats with streptozotocin-induced diabetes by rice bran oil supplementation. Ann N Y Acad Sci 2005; 1042: 365-71.
22. Park KS, Kim JH, Kim MS, et al. Effects of insulin and antioxidant on plasma 8-hydroxyguanine and tissue 8-hydroxydeoxyguanosine in streptozotocin-induced diabetic rats. Diabetes 2001; 50: 2837-41.
23. Hwang D, Seo S, Kim Y, et al. Selenium acts as an insulin-like molecule for the down-regulation of diabetic symptoms via endoplasmic reticulum stress and insulin signalling proteins in diabetes-induced non-obese diabetic mice. J Bio Sci 2007; 32: 723-35.
24. Traverso N, Menini S, Odetti P, Pronzato MA, Cottalasso D, Marinari UM. Lipoperoxidation in hepatic subcellular compartments of diabetic rats. Free Radic Biol Med 1999; 26: 538-47.
25. Traverso N, Menini S, Odetti P, Pronzato MA, Cottalasso D, Marinari UM. Diabetes impairs the enzymatic disposal of 4-hydroxynonenal in rat liver. Free Radic Biol Med 2002; 32: 350-9.
26. Kelder B, Boyce K, Kriete A, et al. CIDE-A is expressed in liver of old mice and in Type 2 diabetic mouse liver exhibiting steatosis. Comp Hepatol 2007; 6: 4.
27. Dentin R, Hedrick S, Xie J, Yates J 3rd, Montminy M. Hepatic glucose sensing via the CREB coactivator CRTC2. Science 2008; 319: 1402-5.
28. Carmiel-Haggai M, Cederbaum AI, Nieto N. A high-fat diet leads to the progression of non-alcoholic fatty liver disease in obese rats. FASEB J 2005; 19: 136-8.
29. Paradis V, Perlemuter G, Bonvoust F, et al. High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: a potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis. Hepatology 2001; 34: 738-44.
30. Sawant SP, Dnyanmote AV, Shankar K, Limaye PB, Latendresse JR, Mehendale HM. Potentiation of carbon tetrachloride hepatotoxicity and lethality in Type 2 diabetic rats. J Pharmacol Exp Ther 2004; 308: 694-704.
31. Sawant SP, Dnyanmote AV, Warbritton A, Latendresse JR, Mehendale HM. Type 2 diabetic rats are sensitive to thioacetamide hepatotoxicity. Toxicol Appl Pharmacol 2006; 211: 221-32.
32. Ferreira FM, Seiça R, Santos MS, Palmeira CM. Age-related alterations in liver mitochondrial bioenergetics of diabetic Goto-Kakizaki rats. Acta Diabetol 1999; 36: 173-7.
33. Murao K, Yu X, Imachi H, et al. Hyperglycemia suppresses hepatic scavenger receptor class B Type I expression. Am J Physiol Endocrinol Metab 2008; 294: E78-87.
34. Sahai A, Malladi P, Pan X, et al. Obese and diabetic db/db mice develop marked liver fibrosis in a model of nonalcoholic steatohepatitis: role of short-form leptin receptors and osteopontin. Am J Physiol Gastrointest Liver Physiol 2004; 287: G1035-43.
35. Elrod JW, Duranski MR, Langston W, et al. eNOS Gene therapy exacerbates hepatic ischemia-reperfusion injury in diabetes- A role for eNOS uncoupling. Circ Res 2006; 99: 78-85.
36. Aoki K, Nakajima A, Mukasa K, Osawa E, Mori Y, Sekihara H. Prevention of diabetes, hepatic injury, and colon cancer with dehydroepiandrosterone. J Steroid Biochem Mol Biol 2003; 85: 469-72.
37. Fujimoto M, Shimizu N, Kunii K, Martyn JA, Ueki K, Kaneki M. A role for iNOS in fasting hyperglycemia and impaired insulin signaling in the liver of obese diabetic mice. Diabetes 2005; 54:1340-8.
38. Dey A, Cederbaum AI. Induction of cytochrome P450 2E1 [corrected] promotes liver injury in ob/ob mice. Hepatology 2007; 45: 1355-65.
39. Dey A, Caro AA, Cederbaum AI. S-adenosyl methionine protects ob/ob mice from CYP2E1-mediated liver injury. Am J Physiol Gastrointest Liver Physiol 2007; 293: G91-G103.
40. Ling PR, Mueller C, Smith RJ, Bistrian BR. Hyperglycemia induced by glucose infusion causes hepatic oxidative stress and systemic inflammation, but not STAT3 or MAP kinase activation in liver in rats. Metabolism 2003; 52: 868-74.
41. Ling PR, Smith RJ, Bistrian BR. Acute effects of hyperglycemia and hyperinsulinemia on hepatic oxidative stress and the systemic inflammatory response in rats. Laboratory Investigations. Crit Care Med 2007; 35: 555-60.
42. Zhang X, Jiang B, Luo G, Nilsson-Ehle P, Xu N. Hyperglycemia down-regulates apolipoprotein M expression in vivo and in vitro. Biochim Biophys Acta 2007; 1771: 879-82.
43. Nawano M, Ueta K, Oku A, et al. Hyperglycemia impairs the insulin signaling step between PI 3-Kinase and Akt/PKB activations in ZDF rat liver. Biochem Biophys Res Commun 1999; 266: 252-6.
44. Li X, Hansen PA, Xi L, Chandraratna RA, Burant CF. Distinct mechanisms of glucose lowering by specific agonists for peroxisomal proliferator activated receptor γ and retinoic acid x receptors. J Biol Chem 2005; 280: 38317-27.
45. Nakatani Y, Kaneto H, Kawamori D, et al. Modulation of the JNK pathway in liver affects insulin resistance status. J Biol Chem 2004; 279: 45803-9.
46. Qiao L, MacDougald OA, Shao J. CAAT/Enhancer-binding protein α mediates induction of hepatic phosphoenolpyruvate carboxykinase by p38 mitogen-activated protein kinase. J Biol Chem 2006; 281: 24390-7.
47. Cao W, Collins QF, Becker TC, et al. p38 Mitogen-activated protein kinase plays a stimulatory role in hepatic gluconeogenesis. J Biol Chem 2005; 280: 42731-7.
48. Shankar K, Vaidya VS, Corton JC, et al. Activation of PPAR-alpha in streptozotocin-induced diabetes is essential for resistance against acetaminophen toxicity. FASEB J 2003; 17: 1748-50.
49. Shankar K, Vaidya VS, Apte UM, et al. Type I diabetic mice are protected from acetaminophen hepatotoxicity. Toxicol Sci 2003; 73: 220-34.
50. Sukalski KA, Pinto KA, Berntson JL. Decreased susceptibility of liver mitochondria from diabetic rats to oxidative damage and associated increase in alpha-tocopherol. Free Radic Biol Med 1993; 14: 57-65.
51. Santos MS, Santos DL, Palmeira CM, Seiça R, Moreno AJ, Oliveira CR. Brain and liver mitochondria isolated from diabetic Goto-Kakizaki rats show different susceptibility to induced oxidative stress. Diabetes Metab Res Rev 2001; 17: 223-30.
52. Cosso L, Maineri EP, Traverso N, et al. Induction of heme oxygenase 1 in liver of spontaneously diabetic rats. Free Radic Res 2001; 34: 189-91.
53. Payne VA, Arden C, Lange AJ, Agius L. Contributions of glucokinase and phosphofructokinase-2/fructose bisphosphatase-2 to the elevated glycolysis in hepatocytes from Zucker fa/fa rats. Am J Physiol Regul Integr Comp Physiol 2007; 293: R618-25.
54. Arden C, Green AR, Hampson LJ, et al. Increased sensitivity of glycogen synthesis to phosphorylase-a and impaired expression of the glycogen-targeting protein R6 in hepatocytes from insulin-resistant Zucker fa/fa rats. FEBS J 2006; 273: 1989-99.
55. Ishii S, Iizuka K, Miller BC, Uyeda K. Carbohydrate response element binding protein directly promotes lipogenic enzyme gene transcription. Proc Natl Acad Sci USA 2004; 101: 15597-602.
56. Tsatsos NG, Towle HC. Glucose activation of ChREBP in hepatocytes occurs via a two-step mechanism. Biochem Biophys Res Commun 2006; 340: 449-56.
57. Ma L, Robinson LN, Towle HC. ChREBP/Mlx is the principal mediator of glucose-induced gene expression in the liver. J Biol Chem 2006; 281: 28721-30.
58. Rencurel F, Waeber G, Bonny C, et al. cAMP prevents the glucose-mediated stimulation of GLUT2 gene transcription in hepatocytes. Biochem J 1997; 322: 441-8.
59. O'Callaghan BL, Koo SH, Wu Y, Freake HC, Towle HC. Glucose regulation of the Acetyl-CoA carboxylase promoter PI in rat hepatocytes. J Biol Chem 2001; 276: 16033-39.
60. Brocklehurst KJ, Payne VA, Davies RA, et al. Stimulation of Hepatocyte glucose metabolism by novel small molecule glucokinase activators. Diabetes 2004; 53: 535-41.
61. Sauvaget D, Chauffeton V, Dugué-Pujol S, et al. In vitro transcriptional induction of the human apolipoprotein A-II gene by glucose. Diabetes 2004; 53: 672-8.
62. Sakamoto J, Kimura H, Moriyama S, et al. Activation of Human Peroxisome Proliferator-Activated Receptor (PPAR) Subtypes by Pioglitazone. Biochem Biophys Res Commun 2000; 278: 704-11.
63. van Deursen D, Jansen H, Verhoeven AJ. Glucose increases hepatic lipase expression in HepG2 liver cells through upregulation of upstream stimulatory factors 1 and 2. Diabetologia 2008; 51(11): 2078-87.
64. Zang M, Zuccollo A, Hou X, et al. AMP-activated protein kinase is required for the lipid-lowering effect of metformin in insulin-resistant human HepG2 cells. J Biol Chem 2004; 279: 47898-905.
65. Zang M, Xu S, Maitland-Toolan KA, et al. Polyphenols stimulate AMP-activated protein kinase, lower lipids, and inhibit accelerated atherosclerosis in diabetic LDL receptor-deficient mice. Diabetes 2006; 55: 2180-91.
66. Hou X, Xu S, Maitland-Toolan KA, et al. SIRT1 regulates hepatocyte lipid metabolism through activating AMP-activated protein kinase. J Biol Chem 2008; 283: 20015-26.
67. Nakajima K, Yamauchi K, Shigematsu S, et al. Selective attenuation of metabolic branch of insulin receptor down-signaling by high glucose in a hepatoma cell line, HepG2 cells. J Biol Chem 2000; 275: 20880-6.
68. Kuo M, Zilberfarb V, Gangneux N, Christeff N, Issad T. O-glycosylation of FoxO1 increases its transcriptional activity towards the glucose 6-phosphatase gene. FEBS Lett 2008; 582(5): 829-34.
69. Weiss P, Ashwell G, Morell AG, Stockert RJ. Modulation of the asialoglycoprotein receptor in human hepatoma cells: effect of glucose. Hepatology 1994; 19: 432-9.
70. Guan G, Dai P, Shechter I. cDNA cloning and gene expression analysis of human myo-inositol 1-phosphate synthase. Arch Biochem Biophys 2003; 417: 251-9.
71. Briata P, Laurino C, Gherzi R. c-myc gene expression in human cells is controlled by glucose. Biochem Biophys Res Commun 1989; 165: 1123-9.
72. Palmeira CM, Rolo AP, Berthiaume J, Bjork JA, Wallace KB. Hyperglycemia decreases mitochondrial function: the regulatory role of mitochondrial biogenesis. Toxicol Appl Pharmacol 2007; 225: 214-20.
73. Tan J, Yang HS, Patel MS. Regulation of mammalian pyruvate dehydrogenase alpha subunit gene expression by glucose in HepG2 cells. Biochem J 1998; 336: 49-56.
74. Iwasaki Y, Kambayashi M, Asai M, Yoshida M, Nigawara T, Hashimoto K. High glucose alone, as well as in combination with proinflammatory cytokines, stimulates nuclear factor kappa-B-mediated transcription in hepatocytes in vitro. J Diabetes Complications 2007; 21: 56-62.
75. Cheng G, Polito CC, Haines JK, et al. Decrease of intracellular ATP content downregulated UCP2 expression in mouse hepatocytes. Biochem Biophys Res Commun 2003; 308: 573-80.
76. Shao J, Qiao L, Janssen RC, Pagliassotti M, Friedman JE. Chronic hyperglycemia enhances PEPCK gene expression and hepatocellular glucose production via elevated liver activating protein/liver inhibitory protein. Diabetes 2005; 54: 976-84.
77. Sugimoto R, Enjoji M, Kohjima M, et al. High glucose stimulates hepatic stellate cells to proliferate and to produce collagen through free radical production and activation of mitogen-activated protein kinase. Liver Int 2005; 25: 1018-26.
78. Clark JM. The epidemiology of nonalcoholic fatty liver disease in adults. J Clin Gastroenterol 2006; 40: S5-10.
79. Yeh MM, Brunt EM. Pathology of nonalcoholic fatty liver disease. Am J Clin Pathol 2007; 128: 837-47
80. Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with Type 2 diabetes. Clin Gastroenterol Hepatol 2004; 2: 262-5.
81. Fracanzani AL, Valenti L, Bugianesi E, et al. Risk of severe liver disease in nonalcoholic fatty liver disease with normal aminotransferase levels: a role for insulin resistance and diabetes. Hepatology 2008; 48: 792-8.
82. Mofrad P, Contos MJ, Haque M, et al. Clinical and histologic spectrum of nonalcoholic fatty liver disease associated with normal ALT values. Hepatology 2003; 37: 1286-92.
83. Bugianesi E, Manzini P, D'Antico S, et al. Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver. Hepatology 2004; 39: 179-87.
84. Oh SY, Cho YK, Kang MS, et al. The association between increased alanine aminotransferase activity and metabolic factors in nonalcoholic fatty liver disease. Metabolism 2006; 55: 1604-9.
85. Charlton M, Angulo P, Chalasani N, et al. Low circulating levels of dehydroepiandrosterone in histologically advanced nonalcoholic fatty liver disease. Hepatology 2008; 47: 484-92.
86. Miele L, Beale G, Patman G, et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology 2008; 135: 282-91.
87. Gholam PM, Flancbaum L, Machan JT, Charney DA, Kotler DP. Nonalcoholic fatty liver disease in severely obese subjects. Am J Gastroenterol 2007; 102: 399-408.
88. Abrams GA, Kunde SS, Lazenby AJ, Clements RH. Portal fibrosis and hepatic steatosis in morbidly obese subjects: A spectrum of nonalcoholic fatty liver disease. Hepatology 2004; 40: 475-83.
89. Valenti L, Rametta R, Dongiovanni P, et al. Increased expression and activity of the transcription factor FOXO1 in nonalcoholic steatohepatitis. Diabetes 2008; 57: 1355-62.
90. Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-62.
91. Targher G, Bertolini L, Padovani R, et al. Prevalence of nonalcoholic fatty liver disease and its association with cardiovascular disease among Type 2 diabetic patients. Diabetes Care 2007; 30: 1212-8.
92. Chatila R, West AB. Hepatomegaly and abnormal liver tests due to glycogenosis in adults with diabetes. Medicine (Baltimore) 1996; 75: 327-33.
93. Misu H, Takamura T, Matsuzawa N, et al. Genes involved in oxidative phosphorylation are coordinately upregulated with fasting hyperglycaemia in livers of patients with Type 2 diabetes. Diabetologia 2007; 50: 268-77.
94. Vanhorebeek I, De Vos R, Mesotten D, Wouters PJ, De Wolf-Peeters C, Van den Berghe G. Protection of hepatocyte mitochondrial ultrastructure and function by strict blood glucose control with insulin in critically ill patients. Lancet 2005; 365: 53-9.
95. Belfort R, Harrison SA, Brown K, et al. A placebo-controlled trial of pioglitazone in subjects with nonalcoholic steatohepatitis. N Engl J Med 2006; 355: 2297-307.
96. Gastaldelli A, Miyazaki Y, Pettiti M, et al. The effect of rosiglitazone on the liver: decreased gluconeogenesis in patients with Type 2 diabetes. J Clin Endocrinol Metab 2006; 91: 806-12.
97. Iozzo P, Turpeinen AK, Takala T, et al. Defective liver disposal of free fatty acids in patients with impaired glucose tolerance. J Clin Endocrinol Metab 2004; 89: 3496-502.
98. Todorova B, Kubaszek A, Pihlajamäki J, et al. The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to Type 2 diabetes mellitus: the Finnish Diabetes Prevention Study. J Clin Endocrinol Metab 2004; 89: 2019-23.
99. Iozzo P, Hallsten K, Oikonen V, et al. Insulin-mediated hepatic glucose uptake is impaired in Type 2 diabetes: evidence for a relationship with glycemic control. J Clin Endocrinol Metab 2003; 88: 2055-60.
100. Bischof MG, Krssak M, Krebs M, et al. Effects of short-term improvement of insulin treatment and glycemia on hepatic glycogen metabolism in Type 1 diabetes. Diabetes 2001; 50: 392-8.
101. Clore JN, Stillman J, Sugerman H. Glucose-6-phosphatase flux in vitro is increased in Type 2 diabetes. Diabetes 2000; 49: 969-74.
102. Jaskiewicz K, Rzepko R, Sledzinski Z. Fibrogenesis in fatty liver associated with obesity and diabetes mellitus Type 2. Dig Dis Sci 2008; 53: 785-8.