Stereological assessment of pancreatic beta-cell mass development in male Zucker Diabetic Fatty (ZDF) rats: correlation with pancreatic beta-cell function.
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.
Paulsen
Sarah Juel
SJ
Rheoscience A/S, Roedovre, Denmark.
Vrang
Niels
N
Larsen
Leif Kongskov
LK
Larsen
Philip Just
PJ
Jelsing
Jacob
J
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
D001786:Blood Glucose; D007328:Insulin
Proc Natl Acad Sci U S A. 1994 Nov 8;91(23):10878-82
7971976
Metabolism. 2000 May;49(5):684-8
10831184
Diabetes. 1998 Mar;47(3):358-64
9519740
J Microsc. 1999 Mar;193(Pt 3):199-211
10348656
Diabetes. 2001 May;50(5):1021-9
11334404
Am J Physiol Endocrinol Metab. 2007 Dec;293(6):E1730-5
17895283
Diabetes. 2001 Jan;50(1):63-8
11147796
Physiol Rev. 2007 Oct;87(4):1409-39
17928588
Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E549-60
17003242
Am J Physiol Endocrinol Metab. 2008 Feb;294(2):E271-83
18029442
Horm Metab Res. 1999 Nov;31(11):610-5
10598829
Diabetes Obes Metab. 2005 Jul;7(4):307-17
15955116
Diabetes. 2007 Apr;56(4):930-9
17395740
Diabetes. 2002 May;51(5):1437-42
11978640
Diabetes. 1999 Sep;48(9):1801-6
10480611
Am J Pathol. 2003 Jul;163(1):21-8
12819007
Trends Mol Med. 2008 Apr;14(4):161-8
18353723
Diabetes Care. 1999 Sep;22(9):1462-70
10480510
J Biol Chem. 1996 Mar 8;271(10):5633-7
8621426
Proc Natl Acad Sci U S A. 1998 Mar 3;95(5):2498-502
9482914
Endocrinology. 2003 Sep;144(9):4154-63
12933690
J Microsc. 1987 Sep;147(Pt 3):229-63
3430576
Exp Clin Endocrinol Diabetes. 2001;109(5):273-82
11507651
Diabetes. 2003 Jul;52(7):1716-22
12829638
Ilar News. 1990 Jan;32(3):13-15
34191867