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 mi ld hyperglycemia with a reduction of beta-cell mass, The mechanism for isle t structural changes in this model and whether the changes are affected by metabolic control are not known. In the present study, we examined the proc ess of islet changes in male GK rats aged 6, 8, 12, 24, and 36 weeks. Treat ment 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 t he increase was significantly (P < .01) smaller in GK rats versus at 8 week s of age. Thereafter, the beta-cell mass decreased in GK rats, whereas it r emained constant in controls. Voglibose treatment significantly(P < .01) in hibited the reduction of beta-cell mass in GK rats. Proliferative activity of beta cells as measured by bromodeoxyuridine (BrdU) uptake was significan tly(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 trea tment. The present study thus demonstrates a progressive loss of 8 cells in GK rats that was mitigated by Voglibose treatment. We consider that the be ta-cell loss in GK rats was due to an early impairment in proliferative act ivity and reduced survival. Voglibose did not appear to stimulate beta-cell proliferation, but exerted its effect via a reduction of hyperglycemia. Co pyright (C) 2000 by W.B. Saunders Company.