Disordered expression of the sucrase-isomaltase complex in the small intestine in Otsuka Long-Evans Tokushima fatty rats, a model of non-insulin-dependent diabetes mellitus with insulin resistance

To clarify the relationship between diabetes mellitus and carbohydrate dige stion, the activities of sucrase and isomaltase, which form a complex enzym e (SI complex) on the brush border membranes, were compared in the progress ion of diabetes mellitus in Otsuka Long-Evans Tokushima fatty (OLETF) rats, a model of human non-insulin-dependent diabetes mellitus with insulin resi stance, and Long-Evans Tokushima Otsuka (LETO) rats as non-diabetic control s. Until 40 weeks of age, OLETF rats were obese and had a high plasma gluco se level, compared to age-matched LETO rats, but the sucrase and isomaltase activities showed no significant differences between the two strains. Oral glucose tolerance test revealed that during 40-48 weeks of age, NIDDM beca me very severe with advancing insulin resistance in OLETF rats. In OLETF ra ts, in contrast to LETO rats, at 48 weeks of age, abnormal increases in the sucrase and isomaltase activities occurred, along with a remarkable decrea se in body weight and a further great increase in the plasma glucose level in the non-fasting state. Hyperinsulinemia occurred in 20-week-old OLETF ra ts; however, at 40 and 48 weeks of age, the plasma insulin level in the non -fasting state in OLETF rats was not significantly different from that in L ETO rats. The level of mRNA encoding the SI complex increased abnormally in 48-week-old OLETF rats. These results suggest that the advance of insulin resistance leads to an increase in the expression of the SI complex on the transcriptional level. (C) 1999 Elsevier Science B.V. All rights reserved.