title: Stereological assessment of pancreatic beta-cell mass development in male Zucker Diabetic Fatty (ZDF) rats: correlation with pancreatic beta-cell function.
abstract: The present study was initiated to improve our understanding of pancreatic beta-cell dynamics in male Zucker Diabetic Fatty (ZDF) rats and hence provide a framework for future diabetes studies in this animal model. Male ZDF rats from 6, 8, 10, 12, 14, 16, 20 and 26 weeks of age were subjected to an oral glucose tolerance test (OGTT). The animals were then euthanized and pancreases were removed for morphometric analyses of pancreatic beta-cell mass. As evident by a marked fourfold increase in insulin secretion, insulin resistance developed rapidly from 6 to 8 weeks of age. Simultaneously, the pancreatic beta-cell mass expanded from 6.17 ± 0.41 mg at 6 weeks of age, reaching a maximum of 16.5 ± 2.5 mg at 16 weeks of age, at which time pancreatic beta-cell mass gradually declined. The corresponding changes in glucose/insulin homeostasis were analysed using a standard insulin sensitivity index (ISI), an area under the curve (AUC) glucose-insulin index, or simple semi-fasted glucose levels. The study demonstrated that male ZDF rats underwent rapid changes in pancreatic beta-cell mass from the onset of insulin resistance to frank diabetes coupled directly to marked alterations in glucose/insulin homeostasis. The study underscores the need for a critical co-examination of glucose homeostatic parameters in studies investigating the effects of novel anti-diabetic compounds on pancreatic beta-cell mass in the male ZDF rat. A simple assessment of fasting glucose levels coupled with information about age can provide a correct indication of the actual pancreatic beta-cell mass and the physiological state of the animal.
authors.affiliation: Rheoscience A/S, Roedovre, Denmark.
authors.forename: Sarah Juel
authors.initials: SJ
authors.lastname: Paulsen
authors.forename: Niels
authors.initials: N
authors.lastname: Vrang
authors.forename: Leif Kongskov
authors.initials: LK
authors.lastname: Larsen
authors.forename: Philip Just
authors.initials: PJ
authors.lastname: Larsen
authors.forename: Jacob
authors.initials: J
authors.lastname: Jelsing
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000473:pathology / Q000503:physiopathology*; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000473:pathology*; D008297:Male; D010179:Pancreas / Q000166:cytology* / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D001786:Blood Glucose; D007328:Insulin
references.citation: Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10878-82
references.pmid: 7971976
references.citation: Metabolism. 2000 May;49(5):684-8
references.pmid: 10831184
references.citation: Diabetes. 1998 Mar;47(3):358-64
references.pmid: 9519740
references.citation: J Microsc. 1999 Mar;193(Pt 3):199-211
references.pmid: 10348656
references.citation: Diabetes. 2001 May;50(5):1021-9
references.pmid: 11334404
references.citation: Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1730-5
references.pmid: 17895283
references.citation: Diabetes. 2001 Jan;50(1):63-8
references.pmid: 11147796
references.citation: Physiol Rev. 2007 Oct;87(4):1409-39
references.pmid: 17928588
references.citation: Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E549-60
references.pmid: 17003242
references.citation: Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E271-83
references.pmid: 18029442
references.citation: Horm Metab Res. 1999 Nov;31(11):610-5
references.pmid: 10598829
references.citation: Diabetes Obes Metab. 2005 Jul;7(4):307-17
references.pmid: 15955116
references.citation: Diabetes. 2007 Apr;56(4):930-9
references.pmid: 17395740
references.citation: Diabetes. 2002 May;51(5):1437-42
references.pmid: 11978640
references.citation: Diabetes. 1999 Sep;48(9):1801-6
references.pmid: 10480611
references.citation: Am J Pathol. 2003 Jul;163(1):21-8
references.pmid: 12819007
references.citation: Trends Mol Med. 2008 Apr;14(4):161-8
references.pmid: 18353723
references.citation: Diabetes Care. 1999 Sep;22(9):1462-70
references.pmid: 10480510
references.citation: J Biol Chem. 1996 Mar 8;271(10):5633-7
references.pmid: 8621426
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: J Microsc. 1987 Sep;147(Pt 3):229-63
references.pmid: 3430576
references.citation: Exp Clin Endocrinol Diabetes. 2001;109(5):273-82
references.pmid: 11507651
references.citation: Diabetes. 2003 Jul;52(7):1716-22
references.pmid: 12829638
references.citation: Ilar News. 1990 Jan;32(3):13-15
references.pmid: 34191867