title: High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice.
abstract: Both short- (1 wk) and long-term (2-12 mo) high-fat diet (HFD) studies reveal enhanced β-cell mass due to increased β-cell proliferation. β-Cell proliferation following HFD has been postulated to occur in response to insulin resistance; however, whether HFD can induce β-cell proliferation independent of insulin resistance has been controversial. To examine the kinetics of HFD-induced β-cell proliferation and its correlation with insulin resistance, we placed 8-wk-old male C57Bl/6J mice on HFD for different lengths of time and assayed the following: glucose tolerance, insulin secretion in response to glucose, insulin tolerance, β-cell mass, and β-cell proliferation. We found that β-cell proliferation was significantly increased after only 3 days of HFD feeding, weeks before an increase in β-cell mass or peripheral insulin resistance was detected. These results were confirmed by hyperinsulinemic euglycemic clamps and measurements of α-hydroxybutyrate, a plasma biomarker of insulin resistance in humans. An increase in expression of key islet-proliferative genes was found in isolated islets from 1-wk HFD-fed mice compared with chow diet (CD)-fed mice. These data indicate that short-term HFD feeding enhances β-cell proliferation before insulin resistance becomes apparent.
authors: Department of Veterans Affairs Tennessee Valley, Nashville, Tennessee; Departments of Medicine.
authors: Rockann E
authors: RE
authors: Mosser
authors: Department of Veterans Affairs Tennessee Valley, Nashville, Tennessee; Departments of Medicine.
authors: Matthew F
authors: MF
authors: Maulis
authors: Montreal Diabetes Research Center, Research Center of the University of Montreal Hospital Cente, and.
authors: Valentine S
authors: VS
authors: Moullé
authors: Department of Veterans Affairs Tennessee Valley, Nashville, Tennessee; Departments of Medicine.
authors: Jennifer C
authors: JC
authors: Dunn
authors: Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee;
authors: Bethany A
authors: BA
authors: Carboneau
authors: Departments of Medicine.
authors: Kavin
authors: K
authors: Arasi
authors: Metabolon, Inc., Durham, North Carolina.
authors: Kirk
authors: K
authors: Pappan
authors: Montreal Diabetes Research Center, Research Center of the University of Montreal Hospital Cente, and Department of Medicine, University of Montreal, Montreal, Quebec, Canada; and.
authors: Vincent
authors: V
authors: Poitout
authors: Department of Veterans Affairs Tennessee Valley, Nashville, Tennessee; Departments of Medicine, Cell and Developmental Biology, and Molecular Physiology and Biophysics, Vanderbilt University, Nashville, Tennessee; maureen.gannon@vanderbilt.edu.
authors: Maureen
authors: M
authors: Gannon
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004041:Dietary Fats / Q000494:pharmacology; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000209:etiology / Q000378:metabolism; D005951:Glucose Tolerance Test; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
chemical_list: D004041:Dietary Fats
keywords: high-fat diet; insulin resistance; mouse models; β-cell mass; β-cell proliferation
references: Am J Physiol Endocrinol Metab. 2012 Sep 15;303(6):E752-61
references: 22829579
references: FEBS Lett. 2001 Oct 19;507(1):59-66
references: 11682060
references: Diabetes. 2005 Dec;54(12):3530-40
references: 16306372
references: J Intern Med. 2009 Oct;266(4):325-38
references: 19765178
references: Diabetes. 2013 May;62(5):1730-7
references: 23160532
references: Am J Physiol Endocrinol Metab. 2009 May;296(5):E1003-12
references: 19116375
references: Rev Neuropsychiatr Infant. 1966 Dec;14(12):315-7
references: 5988016
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Diabetologia. 2005 Jul;48(7):1350-8
references: 15937671
references: Diabetologia. 2005 Apr;48(4):675-86
references: 15729571
references: Diabetes. 2002 Feb;51 Suppl 1:S138-43
references: 11815473
references: Diabetes. 2009 Jun;58(6):1365-72
references: 19265026
references: Diabetes. 2004 Dec;53 Suppl 3:S215-9
references: 15561913
references: J Mol Endocrinol. 2005 Aug;35(1):39-48
references: 16087720
references: PLoS One. 2010;5(5):e10883
references: 20526369
references: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
references: 12883005
references: Diabetes. 2009 Jun;58(6):1312-20
references: 19228811
references: Dis Model Mech. 2010 Sep-Oct;3(9-10):525-34
references: 20713647
references: Diabetes. 2011 Oct;60(10):2474-83
references: 21911747
references: Am J Physiol Endocrinol Metab. 2002 Oct;283(4):E738-44
references: 12217891
references: Diabetes. 1991 Jan;40(1):82-7
references: 2015977
references: Diabetes. 2008 Nov;57(11):3069-77
references: 18728229
references: Diabetes. 1988 Sep;37(9):1163-7
references: 3044882
references: Diabetologia. 2010 Nov;53(11):2369-79
references: 20628728
references: Diabetes. 2003 Jan;52(1):102-10
references: 12502499
references: Acta Physiol Lat Am. 1977;27(1):7-15
references: 616173
references: Endocrinology. 2011 Dec;152(12):4589-600
references: 21952247
references: Am J Physiol Endocrinol Metab. 2013 Jul 1;305(1):E149-59
references: 23673159
references: J Proteome Res. 2013 Oct 4;12(10):4577-84
references: 23984841
references: Anal Chem. 2009 Aug 15;81(16):6656-67
references: 19624122
references: Open Endocrinol J. 2010;4:null
references: 24339840
references: Am J Physiol Endocrinol Metab. 2009 Oct;297(4):E849-55
references: 19638507
references: Science. 2009 May 22;324(5930):1029-33
references: 19460998
references: Mol Cell Biol. 2008 May;28(9):3076-87
references: 18285455
references: Diabetes. 2008 Jul;57(7):1790-9
references: 18398139
references: Am J Physiol Endocrinol Metab. 2014 Jun 15;306(12):E1460-7
references: 24760991
references: PLoS One. 2008;3(2):e1668
references: 18301746
references: Mol Endocrinol. 2014 Sep;28(9):1435-47
references: 25073103
references: Diabetologia. 2013 Jul;56(7):1638-48
references: 23620060
references: Diabetes. 2005 Sep;54(9):2557-67
references: 16123343
references: Mol Endocrinol. 2006 Aug;20(8):1853-66
references: 16556734
references: PLoS One. 2012;7(9):e46057
references: 23049932
references: Diabetes. 2009 Nov;58(11):2607-15
references: 19720802