Pressure pain precedes development of type 2 disease in Zucker rat model of diabetes.
Decreased hind limb pressure pain threshold (PPT) is an early indicator of insulinopenia and neuropathy developing in STZ-rat models of type 1 diabetes and pre-diabetes. To test if pain on pressure is also a hallmark of compensated insulin resistance and type 2 diabetes in this work we measured PPT of Zucker lean (ZL), Zucker fatty (ZF) and Zucker fatty diabetic rats (ZDF; 8 animals per group). Using clinically accepted cut-off values for diagnosis of human diabetes and pre-diabetes, at 6th week of age (the study entry), all animals maintained random blood glucose within a normal range (< 7.9 mM). Over the following 4 weeks, the random glucose remained normal in lean and ZF rats; it however crossed 11 mM cut-off for the diagnosis of diabetes in all ZDF rats. With no detectable relation to blood glucose levels or changes throughout the study, lean, ZF and ZDF rats maintained respectively highest, intermediate and lowest PPT levels (83+/-1, 70+/-1 and 59+/-1 g; mean values for all tests per group). Thus in Zucker rat model, type 2 diabetes-associated impairment of nerve function precedes the development of hyperglycemia. Furthermore, since normoglycemic, but displaying decreased PPT, ZF rats were strongly hyperinsulinemic (plasma insulin concentration 30+/-4 ng/ml vs. 2.4+/-0.3 ng/ml in lean rats) these data suggest that hyperinsulinemia compensating for glucose metabolism might not restore compromised nerve function.
Romanovsky
Dmitry
D
Department of Anesthesiology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Walker
James C
JC
Dobretsov
Maxim
M
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005215:Fasting / Q000502:physiology; D008297:Male; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology*; D011312:Pressure / Q000009:adverse effects*; D051381:Rats; D011924:Rats, Zucker
D001786:Blood Glucose
Diabetes Care. 2008 Jan;31 Suppl 1:S55-60
18165338
J Peripher Nerv Syst. 2004 Jun;9(2):62-9
15104693
Obes Res. 2005 Jun;13(6):991-9
15976141
Diabetes Care. 2004 Jun;27(6):1458-86
15161806
Atherosclerosis. 2000 Feb;148(2):231-41
10657558
Diabetes Care. 1979 Sep-Oct;2(5):409-13
510139
Am J Physiol. 1985 Feb;248(2 Pt 1):E188-93
3881986
Brain Res Brain Res Rev. 1995 Jan;20(1):47-67
7711767
Diabetes Obes Metab. 2008 Jan;10(1):64-74
17970755
Nat Rev Neurosci. 2008 Jan;9(1):36-45
18094705
Diabetologia. 1987 Aug;30(8):653-8
2820821
Metabolism. 1999 Jun;48(6):701-6
10381143
Ann Intern Med. 1995 Apr 15;122(8):561-8
7887548
Neurologist. 2008 Jan;14(1):23-9
18195653
Diabetes. 2006 May;55(5):1430-5
16644701
Muscle Nerve. 1999 Nov;22(11):1564-70
10514235
Metabolism. 2000 May;49(5):684-8
10831184
J Pharmacol Exp Ther. 1997 Oct;283(1):366-74
9336345
N Engl J Med. 2003 Jan 30;348(5):383-93
12556541
Pain. 2003 Jan;101(1-2):187-92
12507713
Neurobiol Dis. 2006 Nov;24(2):384-94
16935517
N Engl J Med. 2006 Feb 9;354(6):545-8
16467539
World J Gastroenterol. 2007 Jan 14;13(2):175-91
17226897
Diabetes. 2001 Jan;50(1):63-8
11147796
Am J Physiol Endocrinol Metab. 2005 Jul;289(1):E113-22
15727946
Exp Neurol. 1996 Aug;140(2):198-205
8690062
Muscle Nerve. 2007 Oct;36(4):536-41
17626290
Diabetologia. 2006 Aug;49(8):1711-21
16802130
Diabetes. 1995 Dec;44(12):1447-57
7589853
Diabetes Care. 1998 Aug;21(8):1221-5
9702423
J Neurophysiol. 1994 Aug;72(2):883-9
7983543