title: Beta cell dysfunction and insulin resistance.
abstract: Beta cell dysfunction and insulin resistance are inherently complex with their interrelation for triggering the pathogenesis of diabetes also somewhat undefined. Both pathogenic states induce hyperglycemia and therefore increase insulin demand. Beta cell dysfunction results from inadequate glucose sensing to stimulate insulin secretion therefore elevated glucose concentrations prevail. Persistently elevated glucose concentrations above the physiological range result in the manifestation of hyperglycemia. With systemic insulin resistance, insulin signaling within glucose recipient tissues is defective therefore hyperglycemia perseveres. Beta cell dysfunction supersedes insulin resistance in inducing diabetes. Both pathological states influence each other and presumably synergistically exacerbate diabetes. Preserving beta cell function and insulin signaling in beta cells and insulin signaling in the glucose recipient tissues will maintain glucose homeostasis.
authors.affiliation: Diabetes Discovery Platform, South African Medical Research Council Cape Town, South Africa.
authors.forename: Marlon E
authors.initials: ME
authors.lastname: Cerf
keywords: beta cell compensation; diabetes; obesity; oxidative stress; proliferation
references.citation: Biochem J. 2012 Jan 15;441(2):523-40
references.pmid: 22187934
references.citation: Autophagy. 2009 Oct;5(7):1055-6
references.pmid: 19657235
references.citation: Diabetes. 2005 Mar;54(3):603-8
references.pmid: 15734833
references.citation: Eur J Pharmacol. 2007 Jul 30;568(1-3):269-77
references.pmid: 17573071
references.citation: Diabetes. 2008 Mar;57(3):645-53
references.pmid: 18071026
references.citation: Science. 2008 Nov 21;322(5905):1250-4
references.pmid: 19023081
references.citation: Diabetes. 1989 Jan;38(1):49-53
references.pmid: 2642434
references.citation: Cell Metab. 2011 Apr 6;13(4):440-449
references.pmid: 21459328
references.citation: Diabetes Obes Metab. 2002 Jan;4(1):56-9
references.pmid: 11874443
references.citation: Diabetes. 1973 Sep;22(9):687-93
references.pmid: 4125576
references.citation: Am J Transplant. 2008 Jan;8(1):183-92
references.pmid: 18021279
references.citation: Diabetologia. 1998 Dec;41(12):1474-81
references.pmid: 9867215
references.citation: J Proteome Res. 2012 Jul 6;11(7):3520-32
references.pmid: 22578083
references.citation: Br J Obstet Gynaecol. 1978 Nov;85(11):818-20
references.pmid: 363135
references.citation: Diabetes Care. 2010 Jul;33(7):1561-6
references.pmid: 20200305
references.citation: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7475-80
references.pmid: 11404474
references.citation: J Nutr. 1987 Feb;117(2):376-82
references.pmid: 3559752
references.citation: Endocrinology. 1995 Dec;136(12):5461-8
references.pmid: 7588296
references.citation: Int J Exp Pathol. 2010 Jun;91(3):288-301
references.pmid: 20384904
references.citation: Diabetes. 2011 Nov;60(11):2710-9
references.pmid: 21984579
references.citation: PLoS One. 2013;8(1):e54059
references.pmid: 23342074
references.citation: Mol Biol Rep. 2012 Jun;39(6):6781-9
references.pmid: 22302392
references.citation: Nat Genet. 2012 May 13;44(6):659-69
references.pmid: 22581228
references.citation: Pancreas. 2007 Apr;34(3):347-53
references.pmid: 17414058
references.citation: Int J Endocrinol. 2012;2012:516718
references.pmid: 22577380
references.citation: Diabetes. 2006 Dec;55(12):3470-7
references.pmid: 17130494
references.citation: Diabetes Obes Metab. 2012 Sep;14(9):835-41
references.pmid: 22510250
references.citation: Cell. 2010 Mar 19;140(6):900-17
references.pmid: 20303879
references.citation: Diabetes. 2010 Oct;59(10):2340-8
references.pmid: 20876724
references.citation: Endocrine. 2013 Aug;44(1):87-98
references.pmid: 23109223
references.citation: Diabetes Obes Metab. 2010 Oct;12 Suppl 2:20-6
references.pmid: 21029296
references.citation: Diabetologia. 2008 Jul;51(7):1100-10
references.pmid: 18504548
references.citation: J Biol Chem. 2004 Oct 8;279(41):42351-4
references.pmid: 15258147
references.citation: Growth Factors. 1994;10(2):115-26
references.pmid: 7520714
references.citation: Diabetes Obes Metab. 2010 Oct;12 Suppl 2:15-9
references.pmid: 21029295
references.citation: PLoS Med. 2006 Feb;3(2):e17
references.pmid: 16354107
references.citation: PLoS Biol. 2007 Jul;5(7):e163
references.pmid: 17535113
references.citation: PLoS One. 2012;7(5):e33254
references.pmid: 22606220
references.citation: Diabetes. 2000 Aug;49(8):1341-6
references.pmid: 10923635
references.citation: Eur J Endocrinol. 2009 Feb;160(2):185-91
references.pmid: 19004984
references.citation: Am J Physiol. 1971 Jul;221(1):202-8
references.pmid: 4933588
references.citation: ISRN Endocrinol. 2012;2012:627270
references.pmid: 22988521
references.citation: Diabetes. 2008 Nov;57(11):2889-98
references.pmid: 18971436
references.citation: Endocrinology. 1997 Apr;138(4):1736-41
references.pmid: 9075738
references.citation: Endocrinology. 2003 Jun;144(6):2717-27
references.pmid: 12746336
references.citation: Diabetes. 2008 Jun;57(6):1584-94
references.pmid: 18334605
references.citation: N Engl J Med. 2010 Dec 9;363(24):2339-50
references.pmid: 21142536
references.citation: PLoS One. 2012;7(5):e36675
references.pmid: 22586489
references.citation: Cell Biochem Biophys. 2007;48(2-3):139-46
references.pmid: 17709883
references.citation: Diabetes. 2002 Dec;51 Suppl 3:S326-32
references.pmid: 12475771
references.citation: Diabetes. 2005 Mar;54(3):727-35
references.pmid: 15734849
references.citation: J Mol Med (Berl). 2005 Jun;83(6):429-39
references.pmid: 15759102
references.citation: Endocr Rev. 2008 May;29(3):351-66
references.pmid: 18048763
references.citation: Diabetes. 2009 Jun;58(6):1365-72
references.pmid: 19265026
references.citation: Am J Transplant. 2007 Mar;7(3):707-13
references.pmid: 17229069
references.citation: PLoS One. 2011 Mar 30;6(3):e18134
references.pmid: 21479217
references.citation: Mol Cell Biochem. 2003 Apr;246(1-2):155-62
references.pmid: 12841357
references.citation: Proc Natl Acad Sci U S A. 2009 Nov 10;106(45):19090-5
references.pmid: 19855005
references.citation: J Clin Invest. 2004 Sep;114(6):828-36
references.pmid: 15372107
references.citation: J Clin Invest. 2006 Jul;116(7):1756-60
references.pmid: 16823472
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):8977-82
references.pmid: 17416680
references.citation: Diabetes. 2001 May;50(5):1021-9
references.pmid: 11334404
references.citation: Diabetes Obes Metab. 2012 Nov;14(11):983-9
references.pmid: 22594400
references.citation: Diabetologia. 1994 Oct;37(10):1044-50
references.pmid: 7851683
references.citation: Diabetologia. 2012 Aug;55(8):2214-25
references.pmid: 22581040
references.citation: Diabetologia. 2009 Jun;52(6):1083-6
references.pmid: 19367387
references.citation: Nat Rev Endocrinol. 2009 Dec;5(12):682-93
references.pmid: 19924153
references.citation: Nat Genet. 2010 Feb;42(2):105-16
references.pmid: 20081858
references.citation: Rev Endocr Metab Disord. 2007 Jun;8(2):95-104
references.pmid: 17680370
references.citation: Diabetologia. 2007 Dec;50(12):2486-94
references.pmid: 17906960
references.citation: Diabetes. 2003 Jan;52(1):1-8
references.pmid: 12502486
references.citation: Physiol Rev. 2005 Oct;85(4):1255-70
references.pmid: 16183912
references.citation: Diabetes Metab. 2009 Apr;35(2):77-84
references.pmid: 19251449
references.citation: Diabetes. 2009 Sep;58(9):2059-69
references.pmid: 19502415
references.citation: Am J Physiol Endocrinol Metab. 2004 Nov;287(5):E1024-31
references.pmid: 15251867
references.citation: Trends Endocrinol Metab. 2010 May;21(5):261-7
references.pmid: 20096598
references.citation: Cell Metab. 2008 Oct;8(4):325-32
references.pmid: 18840363
references.citation: Diabetes. 2001 Feb;50 Suppl 1:S154-9
references.pmid: 11272180
references.citation: Dev Dyn. 2004 Apr;229(4):813-25
references.pmid: 15042705
references.citation: J Mol Med (Berl). 2011 Aug;89(8):785-98
references.pmid: 21487676
references.citation: Diabetes. 2010 May;59(5):1192-201
references.pmid: 20150285
references.citation: Cell Metab. 2009 Dec;10(6):455-65
references.pmid: 19945403
references.citation: Diabetologia. 2012 May;55(5):1390-9
references.pmid: 22311418
references.citation: J Clin Invest. 2007 Sep;117(9):2553-61
references.pmid: 17786244
references.citation: PPAR Res. 2007;2007:95974
references.pmid: 17389767
references.citation: Horm Res. 2005;64 Suppl 3:8-15
references.pmid: 16439839
references.citation: Diabetes Care. 2007 Nov;30(11):2916-21
references.pmid: 17666465
references.citation: Diabetes. 1995 Mar;44(3):249-56
references.pmid: 7883109
references.citation: Clin Endocrinol (Oxf). 2012 Oct;77(4):508-12
references.pmid: 22640465
references.citation: Ups J Med Sci. 2000;105(2):7-15
references.pmid: 11095102
references.citation: Diabetologia. 2012 May;55(5):1380-9
references.pmid: 22327314
references.citation: J Biol Chem. 2005 May 20;280(20):19977-85
references.pmid: 15774466
references.citation: J Biol Chem. 2012 Jun 29;287(27):23236-45
references.pmid: 22589549
references.citation: J Clin Invest. 2001 Jul;108(1):63-72
references.pmid: 11435458
references.citation: Diabetes Obes Metab. 2008 Nov;10 Suppl 4:32-42
references.pmid: 18834431
references.citation: Biochem J. 2012 Aug 1;445(3):349-59
references.pmid: 22587331
references.citation: Cell. 2012 Sep 14;150(6):1223-34
references.pmid: 22980982
references.citation: Cell. 2012 Mar 16;148(6):1160-71
references.pmid: 22424227
references.citation: Am J Pathol. 2007 Aug;171(2):513-24
references.pmid: 17620365
references.citation: Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E475-83
references.pmid: 17519280
references.citation: Epigenetics. 2012 Aug;7(8):841-52
references.pmid: 22810088
references.citation: Diabetologia. 2013 Mar;56(3):508-19
references.pmid: 23262664
references.citation: World J Diabetes. 2011 Sep 15;2(9):149-57
references.pmid: 21954419
references.citation: Am J Physiol Endocrinol Metab. 2012 Jan 15;302(2):E254-64
references.pmid: 22045312
references.citation: FASEB J. 2011 Aug;25(8):2592-603
references.pmid: 21525490
references.citation: J Clin Invest. 2006 Jul;116(7):1793-801
references.pmid: 16823477
references.citation: Diabetes. 2004 Dec;53 Suppl 3:S225-32
references.pmid: 15561916
references.citation: PLoS One. 2013;8(1):e52862
references.pmid: 23300997
references.citation: Nat Clin Pract Endocrinol Metab. 2007 Nov;3(11):758-68
references.pmid: 17955017
references.citation: J Clin Endocrinol Metab. 2012 Sep;97(9):3197-206
references.pmid: 22745242
references.citation: Cell Metab. 2010 May 5;11(5):349-52
references.pmid: 20444416
references.citation: Nat Genet. 2010 Jul;42(7):579-89
references.pmid: 20581827
references.citation: Pflugers Arch. 2010 Sep;460(4):703-18
references.pmid: 20652307
references.citation: Dev Cell. 2007 May;12(5):817-26
references.pmid: 17488631
references.citation: Biochem Soc Trans. 2008 Jun;36(Pt 3):343-7
references.pmid: 18481954
references.citation: Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2498-502
references.pmid: 9482914
references.citation: Endocrinology. 2003 Sep;144(9):4154-63
references.pmid: 12933690
references.citation: Nat Rev Immunol. 2011 Feb;11(2):98-107
references.pmid: 21233852
references.citation: Biochem Pharmacol. 2011 Feb 15;81(4):471-7
references.pmid: 21111713
references.citation: Diabetes. 2005 Sep;54(9):2557-67
references.pmid: 16123343
references.citation: Cell Metab. 2012 Apr 4;15(4):518-33
references.pmid: 22465073
references.citation: Diabetes. 2001 Sep;50(9):2021-8
references.pmid: 11522667
references.citation: J Transplant. 2012;2012:230870
references.pmid: 22919462
references.citation: Diabetologia. 2003 Oct;46(10):1297-312
references.pmid: 13680127
references.citation: Dev Biol. 2008 May 15;317(2):531-40
references.pmid: 18394599
references.citation: Braz J Med Biol Res. 2011 Oct;44(10):966-72
references.pmid: 21876873
references.citation: Nat Rev Mol Cell Biol. 2008 Mar;9(3):193-205
references.pmid: 18200017
references.citation: Diabetologia. 2010 Feb;53(2):321-30
references.pmid: 19855953
references.citation: Diabetes. 2013 May;62(5):1738-45
references.pmid: 23274905
references.citation: Trends Biochem Sci. 2011 Jan;36(1):30-8
references.pmid: 20728362
references.citation: Trends Mol Med. 2010 Sep;16(9):407-16
references.pmid: 20728409
references.citation: PLoS One. 2012;7(5):e33023
references.pmid: 22606219
references.citation: Horm Metab Res. 2004 Nov-Dec;36(11-12):811-21
references.pmid: 15655713
references.citation: Cell. 2012 Mar 2;148(5):852-71
references.pmid: 22385956
references.citation: Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E271-83
references.pmid: 18029442
references.citation: Mol Cell. 2000 Jul;6(1):87-97
references.pmid: 10949030
references.citation: Sci Signal. 2010 Feb 23;3(110):pe7
references.pmid: 20179270
references.citation: Diabetes. 2007 Jul;56(7):1792-801
references.pmid: 17400928
references.citation: Nature. 2004 May 6;429(6987):41-6
references.pmid: 15129273
references.citation: J Clin Invest. 2004 Oct;114(7):963-8
references.pmid: 15467835
references.citation: Hum Mol Genet. 2009 Jul 1;18(13):2388-99
references.pmid: 19386626
references.citation: Cytokine. 2012 Jul;59(1):65-71
references.pmid: 22579112
references.citation: Biochem Biophys Res Commun. 2005 Apr 8;329(2):726-32
references.pmid: 15737646
references.citation: Mol Cell Endocrinol. 2009 Jan 15;297(1-2):34-40
references.pmid: 18606489
references.citation: Biochem Soc Trans. 2008 Jun;36(Pt 3):357-9
references.pmid: 18481957
references.citation: Am J Clin Nutr. 2010 Mar;91(3):502-9
references.pmid: 20089734
references.citation: Diabetologia. 2001 Aug;44(8):1026-33
references.pmid: 11484081
references.citation: PLoS Genet. 2010 May 27;6(5):e1000970
references.pmid: 20523905
references.citation: Adv Exp Med Biol. 2010;654:77-89
references.pmid: 20217495
references.citation: Endocrinology. 1998 Jun;139(6):2994-3004
references.pmid: 9607811
references.citation: Diabetes. 2006 Sep;55(9):2455-62
references.pmid: 16936193
references.citation: Endocrinology. 1992 Mar;130(3):1459-66
references.pmid: 1537300
references.citation: Cell. 2012 May 25;149(5):1060-72
references.pmid: 22632970
references.citation: Obesity (Silver Spring). 2008 Mar;16(3):522-30
references.pmid: 18239594
references.citation: Am J Physiol Endocrinol Metab. 2005 Apr;288(4):E707-14
references.pmid: 15562255
references.citation: Diabetes. 2005 Dec;54 Suppl 2:S97-107
references.pmid: 16306347
references.citation: Diabetes. 2003 Jan;52(1):102-10
references.pmid: 12502499
references.citation: Pancreas. 1996 May;12(4):334-9
references.pmid: 8740398
references.citation: Endocr Rev. 2006 Dec;27(7):762-78
references.pmid: 17056740
references.citation: Transplantation. 2005 Oct 27;80(8):1003-11
references.pmid: 16278578