The new biology of diabetes

Diabetologia

Volumn 58, Issue 11, 2015, Pages 2459-2468

  Pajvani, Utpal B ^a   Accili, Domenico ^a  

^a NewYork Presbyterian Hospital   (United States)

Author keywords

Beta cell failure; Bile acid; Cholesterol; Dedifferentiation; Diabetes outcome; FOXO; Heart disease; Hepatic glucose production; Lipoprotein; Notch 1; Review

Indexed keywords

BILE ACID; GLUCOKINASE; GLUCOSE 6 PHOSPHATASE; NOTCH RECEPTOR; TRANSCRIPTION FACTOR FOXO; FORKHEAD TRANSCRIPTION FACTOR; GLUCOSE; INSULIN;

ATHEROSCLEROSIS; BIOLOGY; CELL DIFFERENTIATION; DIABETES MELLITUS; GENE EXPRESSION; GLUCONEOGENESIS; HUMAN; INSULIN RESISTANCE; LIPID LIVER LEVEL; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET BETA CELL; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; ANIMAL; LIVER; METABOLISM;

ANIMALS; DIABETES MELLITUS, TYPE 2; FORKHEAD TRANSCRIPTION FACTORS; GLUCOSE; GLUCOSE-6-PHOSPHATASE; HUMANS; INSULIN; INSULIN-SECRETING CELLS; LIVER;

EID: 84942990707     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-015-3722-5     Document Type: Review

References (98)

1. Accili D (2004) Lilly lecture 2003: the struggle for mastery in insulin action: from triumvirate to republic. Diabetes 53:1633–1642
2. Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443
3. Duckworth W, Abraira C, Moritz T et al (2009) Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360:129–139
4. 5-isopropyl biguanide. J Pharmacol Exp Ther 91:157–160
5. Baggio LL, Drucker DJ (2006) Therapeutic approaches to preserve islet mass in type 2 diabetes. Annu Rev Med 57:265–281
6. Accili D, Ahren B, Boitard C, Cerasi E, Henquin JC, Seino S (2010) What ails the beta-cell? Diabetes Obes Metab 12(Suppl 2):1–3
7. Accili D, Arden KC (2004) FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell 117:421–426
8. Haeusler RA, Han S, Accili D (2010) Hepatic FoxO1 ablation exacerbates lipid abnormalities during hyperglycemia. J Biol Chem 285:26861–26868
9. Kitamura YI, Kitamura T, Kruse JP et al (2005) FoxO1 protects against pancreatic beta cell failure through NeuroD and MafA induction. Cell Metab 2:153–163
10. Talchai C, Xuan S, Lin HV, Sussel L, Accili D (2012) Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell 150:1223–1234
11. White MF (2003) Insulin signaling in health and disease. Science 302:1710–1711
12. Rothman DL, Magnusson I, Cline G et al (1995) Decreased muscle glucose transport/phosphorylation is an early defect in the pathogenesis of non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci U S A 92:983–987
13. Kahn BB (1996) Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 45:1644–1654
14. Bearn AG, Billing BH, Sherlock S (1951) Hepatic glucose output and hepatic insulin sensitivity in diabetes mellitus. Lancet 2:698–701
15. O’Brien RM, Lucas PC, Forest CD, Magnuson MA, Granner DK (1990) Identification of a sequence in the PEPCK gene that mediates a negative effect of insulin on transcription. Science 249:533–537
16. Yamamoto KK, Gonzalez GA, Biggs WH 3rd, Montminy MR (1988) Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB. Nature 334:494–498
17. Matsumoto M, Pocai A, Rossetti L, Depinho RA, Accili D (2007) Impaired regulation of hepatic glucose production in mice lacking the forkhead transcription factor Foxo1 in liver. Cell Metab 6:208–216
18. Dong XC, Copps KD, Guo S et al (2008) Inactivation of hepatic Foxo1 by insulin signaling is required for adaptive nutrient homeostasis and endocrine growth regulation. Cell Metab 8:65–76
19. Kubota N, Kubota T, Itoh S et al (2008) Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell Metab 8:49–64
20. Altomonte J, Richter A, Harbaran S et al (2003) Inhibition of Foxo1 function is associated with improved fasting glycemia in diabetic mice. Am J Physiol Endocrinol Metab 285:E718–E728
21. Kitamura T, Nakae J, Kitamura Y et al (2002) The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth. J Clin Invest 110:1839–1847
22. Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: An HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278:1319–1322
23. Ogg S, Paradis S, Gottlieb S et al (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999
24. Haeusler RA, Hartil K, Vaitheesvaran B et al (2014) Integrated control of hepatic lipogenesis versus glucose production requires FoxO transcription factors. Nat Commun 5:5190
25. Haeusler RA, Kaestner KH, Accili D (2010) FoxOs function synergistically to promote glucose production. J Biol Chem 285:35245–35248
26. Kim-Muller JY, Zhao S, Srivastava S et al (2014) Metabolic inflexibility impairs insulin secretion and results in MODY-like diabetes in triple FoxO-deficient mice. Cell Metab 20:593–602
27. Kitamura T, Feng Y, Kitamura YI et al (2006) Forkhead protein FoxO1 mediates Agrp-dependent effects of leptin on food intake. Nat Med 12:534–540
28. Plum L, Lin HV, Dutia R et al (2009) The obesity susceptibility gene Cpe links FoxO1 signaling in hypothalamic pro-opiomelanocortin neurons with regulation of food intake. Nat Med 15:1195–1201
29. Ren H, Orozco IJ, Su Y et al (2012) FoxO1 target Gpr17 activates AgRP neurons to regulate food intake. Cell 149:1314–1326
30. Zhang W, Patil S, Chauhan B et al (2006) FoxO1 regulates multiple metabolic pathways in the liver: effects on gluconeogenic, glycolytic, and lipogenic gene expression. J Biol Chem 281:10105–10117
31. Chakrabarti P, Kandror KV (2009) FoxO1 controls insulin-dependent adipose triglyceride lipase (ATGL) expression and lipolysis in adipocytes. J Biol Chem 284:13296–13300
32. Potente M, Urbich C, Sasaki K et al (2005) Involvement of Foxo transcription factors in angiogenesis and postnatal neovascularization. J Clin Invest 115:2382–2392
33. Tsuchiya K, Tanaka J, Shuiqing Y et al (2012) FoxOs integrate pleiotropic actions of insulin in vascular endothelium to protect mice from atherosclerosis. Cell Metab 15:372–381
34. Kitamura T, Kitamura YI, Kobayashi M et al (2009) Regulation of pancreatic juxtaductal endocrine cell formation by FoxO1. Mol Cell Biol 29:4417–4430
35. Wang Z, York NW, Nichols CG, Remedi MS (2014) Pancreatic beta cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab 19:872–882
36. Nakae J, Kitamura T, Silver DL, Accili D (2001) The forkhead transcription factor Foxo1 (Fkhr) confers insulin sensitivity onto glucose-6-phosphatase expression. J Clin Invest 108:1359–1367
37. Frescas D, Valenti L, Accili D (2005) Nuclear trapping of the forkhead transcription factor FoxO1 via Sirt-dependent deacetylation promotes expression of glucogenetic genes. J Biol Chem 280:20589–20595
38. Ramnanan CJ, Edgerton DS, Rivera N et al (2010) Molecular characterization of insulin-mediated suppression of hepatic glucose production in vivo. Diabetes 59:1302–1311
39. Matveyenko AV, Liuwantara D, Gurlo T et al (2012) Pulsatile portal vein insulin delivery enhances hepatic insulin action and signaling. Diabetes 61:2269–2279
40. Lin HV, Accili D (2011) Hormonal regulation of hepatic glucose production in health and disease. Cell Metab 14:9–19
41. Qu S, Altomonte J, Perdomo G et al (2006) Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism. Endocrinology 147:5641–5652
42. Matsumoto M, Han S, Kitamura T, Accili D (2006) Dual role of transcription factor FoxO1 in controlling hepatic insulin sensitivity and lipid metabolism. J Clin Invest 116:2464–2472
43. Wan M, Leavens KF, Saleh D et al (2011) Postprandial hepatic lipid metabolism requires signaling through Akt2 independent of the transcription factors FoxA2, FoxO1, and SREBP1c. Cell Metab 14:516–527
44. Lu M, Wan M, Leavens KF et al (2012) Insulin regulates liver metabolism in vivo in the absence of hepatic Akt and Foxo1. Nat Med 18:388–395
45. Xiong X, Tao R, DePinho RA, Dong XC (2013) Deletion of hepatic FoxO1/3/4 genes in mice significantly impacts on glucose metabolism through downregulation of gluconeogenesis and upregulation of glycolysis. PLoS One 8:e74340
46. DeFronzo RA (2010) Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: the missing links. The Claude Bernard Lecture 2009. Diabetologia 53:1270–1287
47. Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HA (2008) 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359:1577–1589
48. Caro JJ, Ward AJ, O’Brien JA (2002) Lifetime costs of complications resulting from type 2 diabetes in the U.S. Diabetes Care 25:476–481
49. Rosen CJ (2010) Revisiting the rosiglitazone story—lessons learned. N Engl J Med 363:803–806
50. Bornfeldt KE, Tabas I (2011) Insulin resistance, hyperglycemia, and atherosclerosis. Cell Metab 14:575–585
51. Massa ML, Gagliardino JJ, Francini F (2011) Liver glucokinase: an overview on the regulatory mechanisms of its activity. IUBMB Life 63:1–6
52. Pajvani UB, Qiang L, Kangsamaksin T, Kitajewski J, Ginsberg HN, Accili D (2013) Inhibition of Notch uncouples Akt activation from hepatic lipid accumulation by decreasing mTorc1 stability. Nat Med 19:1054–1060
53. Zhang K, Li L, Qi Y et al (2012) Hepatic suppression of Foxo1 and Foxo3 causes hypoglycemia and hyperlipidemia in mice. Endocrinology 153:631–646
54. Haeusler RA, Pratt-Hyatt M, Welch CL, Klaassen CD, Accili D (2012) Impaired generation of 12-hydroxylated bile acids links hepatic insulin signaling with dyslipidemia. Cell Metab 15:65–74
55. Tao R, Wei D, Gao H, Liu Y, DePinho RA, Dong XC (2011) Hepatic FoxOs regulate lipid metabolism via modulation of expression of the nicotinamide phosphoribosyltransferase gene. J Biol Chem 286:14681–14690
56. Peter A, Stefan N, Cegan A et al (2011) Hepatic glucokinase expression is associated with lipogenesis and fatty liver in humans. J Clin Endocrinol Metab 96:E1126–E1130
57. Matschinsky FM, Zelent B, Doliba NM et al (2011) Research and development of glucokinase activators for diabetes therapy: theoretical and practical aspects. Handb Exp Pharmacol 203:357–401
58. Apelqvist A, Li H, Sommer L et al (1999) Notch signalling controls pancreatic cell differentiation. Nature 400:877–881
59. McCarthy MI (2010) Genomics, type 2 diabetes, and obesity. N Engl J Med 363:2339–2350
60. Pajvani UB, Shawber CJ, Samuel VT et al (2011) Inhibition of Notch signaling ameliorates insulin resistance in a FoxO1-dependent manner. Nat Med 17:961–967
61. Valenti L, Mendoza RM, Rametta R et al (2013) Hepatic notch signaling correlates with insulin resistance and nonalcoholic fatty liver disease. Diabetes 62:4052–4062
62. Purow B (2009) Notch inhibitors as a new tool in the war on cancer: a pathway to watch. Curr Pharm Biotechnol 10:154–160
63. Bi P, Shan T, Liu W et al (2014) Inhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity. Nat Med 20:911–918
64. Liu X, Chhipa RR, Pooya S et al (2014) Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK. Proc Natl Acad Sci U S A 111:E435–E444
65. Staels B, Handelsman Y, Fonseca V (2010) Bile acid sequestrants for lipid and glucose control. Curr Diab Rep 10:70–77
66. Makishima M, Okamoto AY, Repa JJ et al (1999) Identification of a nuclear receptor for bile acids. Science 284:1362–1365
67. Haeusler RA, Astiarraga B, Camastra S, Accili D, Ferrannini E (2013) Human insulin resistance is associated with increased plasma levels of 12alpha-hydroxylated bile acids. Diabetes 62:4184–4191
68. Weyer C, Bogardus C, Mott DM, Pratley RE (1999) The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794
69. Ferrannini E (2010) The stunned beta cell: a brief history. Cell Metab 11:349–352
70. Prentki M, Matschinsky FM, Madiraju SR (2013) Metabolic signaling in fuel-induced insulin secretion. Cell Metab 18:162–185
71. Harbeck MC, Louie DC, Howland J, Wolf BA, Rothenberg PL (1996) Expression of insulin receptor mRNA and insulin receptor substrate 1 in pancreatic islet beta-cells. Diabetes 45:711–717
72. Withers DJ, Sanchez-Gutierrez J, Towery H et al (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391:900–904
73. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR (1999) Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 96:329–339
74. Matschinsky FM (1996) Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm. Diabetes 45:223–241
75. Odegaard ML, Joseph JW, Jensen MV et al (2010) The mitochondrial 2-oxoglutarate carrier is part of a metabolic pathway that mediates glucose- and glutamine-stimulated insulin secretion. J Biol Chem 285:16530–16537
76. Eto K, Tsubamoto Y, Terauchi Y et al (1999) Role of NADH shuttle system in glucose-induced activation of mitochondrial metabolism and insulin secretion. Science 283:981–985
77. Schuit F, de Vos A, Farfari S et al (1997) Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem 272:18572–18579
78. Gheni G, Ogura M, Iwasaki M et al (2014) Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion. Cell Rep 9:661–673
79. Ivarsson R, Quintens R, Dejonghe S et al (2005) Redox control of exocytosis: regulatory role of NADPH, thioredoxin, and glutaredoxin. Diabetes 54:2132–2142
80. MacDonald MJ, Fahien LA, Brown LJ, Hasan NM, Buss JD, Kendrick MA (2005) Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. Am J Physiol Endocrinol Metab 288:E1–E15
81. Buteau J, Shlien A, Foisy S, Accili D (2007) Metabolic diapause in pancreatic beta-cells expressing a gain-of-function mutant of the forkhead protein Foxo1. J Biol Chem 282:287–293
82. Kelley DE, Mandarino LJ (2000) Fuel selection in human skeletal muscle in insulin resistance: a reexamination. Diabetes 49:677–683
83. Puri S, Akiyama H, Hebrok M (2013) VHL-mediated disruption of Sox9 activity compromises beta-cell identity and results in diabetes mellitus. Genes Dev 27:2563–2575
84. Taylor BL, Liu FF, Sander M (2013) Nkx6.1 is essential for maintaining the functional state of pancreatic beta cells. Cell Rep 4:1262–1275
85. Blum B, Roose AN, Barrandon O et al (2014) Reversal of β cell de-differentiation by a small molecule inhibitor of the TGFβ pathway. eLife 3:e02809
86. Burgess SC, He T, Yan Z et al (2007) Cytosolic phosphoenolpyruvate carboxykinase does not solely control the rate of hepatic gluconeogenesis in the intact mouse liver. Cell Metab 5:313–320
87. Henquin JC, Accili D, Ahren B, Boitard C, Seino S, Cerasi E (2011) Long in the shade, glucagon re-occupies centre court. Diabetes Obes Metab 13(Suppl 1):v–viii
88. Dentin R, Liu Y, Koo SH et al (2007) Insulin modulates gluconeogenesis by inhibition of the coactivator TORC2. Nature 449:366–369
89. Dentin R, Hedrick S, Xie J, Yates J 3rd, Montminy M (2008) Hepatic glucose sensing via the CREB coactivator CRTC2. Science 319:1402–1405
90. Liu Y, Dentin R, Chen D et al (2008) A fasting inducible switch modulates gluconeogenesis via activator/coactivator exchange. Nature 456:269–273
91. Ozcan L, Wong CC, Li G et al (2012) Calcium signaling through CaMKII regulates hepatic glucose production in fasting and obesity. Cell Metab 15:739–751
92. Okamoto H, Obici S, Accili D, Rossetti L (2005) Restoration of liver insulin signaling in Insr knockout mice fails to normalize hepatic insulin action. J Clin Invest 115:1314–1322
93. Okamoto H, Nakae J, Kitamura T, Park BC, Dragatsis I, Accili D (2004) Transgenic rescue of insulin receptor-deficient mice. J Clin Invest 114:214–223
94. Lin HV, Plum L, Ono H et al (2010) Divergent regulation of energy expenditure and hepatic glucose production by insulin receptor in agouti-related protein and POMC neurons. Diabetes 59:337–346
95. Konner AC, Janoschek R, Plum L et al (2007) Insulin action in AgRP-expressing neurons is required for suppression of hepatic glucose production. Cell Metab 5:438–449
96. Cherrington AD (2005) The role of hepatic insulin receptors in the regulation of glucose production. J Clin Invest 115:1136–1139
97. Lin HV, Ren H, Samuel VT et al (2011) Diabetes in mice with selective impairment of insulin action in Glut4-expressing tissues. Diabetes 60:700–709
98. Tsuchiya K, Accili D (2013) Liver sinusoidal endothelial cells link hyperinsulinemia to hepatic insulin resistance. Diabetes 62:1478–1489