ID 83482
Author
Shima, Kenji Department of Laboratory Medicine, The University of Tokushima School of Medicine
Zhu, Min Department of Laboratory Medicine, The University of Tokushima School of Medicine
Mizuno, Akira Department of Laboratory Medicine, The University of Tokushima School of Medicine
Keywords
β-cell mass
β-cell proliferation
partial pancreatectomy
nicotinamide
preventive intervention
Content Type
Journal Article
Description
The OLETF rat, a genetic model of spontaneous development of NIDDM, exhibits hyperglycemic obesity with hyperinsulinemia and insulin resistance similar to that in humans. It is still unclear whether a defect in the β-cell proliferation per se is the primary pathogenetic event in this model rat. To clarify this matter, we used partially pancreatectomized rats as a model. Male rats of 6weeks of age were allocated at random to two groups:70% pancreatectomy (Px) and sham-pancreatectomy (sham). Each group was divided into 4 subgroups by the date of sacrifice after surgery.
Sustained hyperglycemia was evident in the Px OLETF rats after surgery. This was associated with insufficient proliferation of β-cells, characterized by a decrease in β-cell labeling with 5-bromo-2'deoxyuridine in proportion to a decrease in β-cell mass and reduction in insulin content in the remnant pancreas. Administration of nicotinamide, however, ameliorated the sustained hyperglycemia by increasing β-cell proliferation. These findings suggest that OLETF rats have a poor capacity for proliferation of pancreatic β-cells, and that this change may be the critical pathogenetic event prior to the onset of overt diabetes.
OLETF rats following long-term caloric restriction and spontaneous exercise training show normal glucose tolerance accompanied by an increase in GIR as shown by a euglycemic clamp. Both exercise training and caloric restriction normalize the abnormalities in the pancreas such as marked hypertrophy of islets and hyperplasia of connective tissues in islets. It is particularly noteworthy that exercise training significantly elevated the β-cell mass / body weight ratio. This evidence obtained from OLETF rats may be of value when the mechanism of diet and exercise effects on diabetic patients are considered.
Journal Title
The journal of medical investigation : JMI
ISSN
13431420
NCID
AA11166929
Volume
46
Issue
3-4
Start Page
121
End Page
129
Sort Key
121
Published Date
1999
Remark
FullText File
language
eng