Inhibition of progressive reduction of islet beta-cell mass in spontaneously diabetic Goto-Kakizaki rats by alpha-glucosidase inhibitor.
The Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, exhibits mild hyperglycemia with a reduction of beta-cell mass. The mechanism for islet structural changes in this model and whether the changes are affected by metabolic control are not known. In the present study, we examined the process of islet changes in male GK rats aged 6, 8, 12, 24, and 36 weeks. Treatment effects with an alpha-glucosidase inhibitor (Voglibose; Takeda, Osaka, Japan) for 24 weeks (12 to 36 weeks of age) were also evaluated. The beta-cell mass increased until 8 weeks of age in both GK and control rats, but the increase was significantly (P < .01) smaller in GK rats versus at 8 weeks of age. Thereafter, the beta-cell mass decreased in GK rats, whereas it remained constant in controls. Voglibose treatment significantly (P < .01) inhibited the reduction of beta-cell mass in GK rats. Proliferative activity of beta cells as measured by bromodeoxyuridine (BrdU) uptake was significantly (P < .05) lower in GK rats versus control rats at 6 and 8 weeks, but the difference disappeared after 12 weeks of age, regardless of Voglibose treatment. The present study thus demonstrates a progressive loss of beta cells in GK rats that was mitigated by Voglibose treatment. We consider that the beta-cell loss in GK rats was due to an early impairment in proliferative activity and reduced survival. Voglibose did not appear to stimulate beta-cell proliferation, but exerted its effect via a reduction of hyperglycemia.
Koyama
M
M
Department of Pathology, Hirosaki University School of Medicine, Hirosaki, Japan.
Wada
R
R
Mizukami
H
H
Sakuraba
H
H
Odaka
H
H
Ikeda
H
H
Yagihashi
S
S
D000375:Aging; D000818:Animals; D001835:Body Weight; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D065089:Glycoside Hydrolase Inhibitors; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D007515:Islets of Langerhans / Q000187:drug effects / Q000254:growth & development / Q000473:pathology*; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007294:Inositol; C102817:voglibose