The effect of a new specific alpha-amylase inhibitor on post-prandial glucose and insulin excursions in normal subjects and Type 2 (non-insulin-dependent) diabetic patients

Abstract

Trestatin (Ro 9-0154), a new specific alpha-amylase inhibitor of microbial origin, was tested in six normal subjects and seven Type 2 (non-insulin-dependent) diabetic patients. In normal subjects the maximal increases in blood glucose following a 115-g starch meal were 2.19 +/- 0.57 mmol/l (mean +/- SEM) with placebo, but 1.32 +/- 0.39 mmol/l with 10 mg, 1.06 +/- 0.26 mmol/l with 20 mg, 0.43 +/- 0.07 mmol/l with 50 mg (p less than 0.05) and 0.26 +/- 0.14 mmol/l with 100 mg (p less than 0.05) Trestatin . The corresponding increases in plasma insulin were 116.5 +/- 19.6 mU/l; 74.8 +/- 17.5 mU/l; 50.7 +/- 8.3 mU/l; 28.7 +/- 6.9 mU/l (p less than 0.05) and 16.5 +/- 3.2 mU/l (p less than 0.05). In the diabetic patients the maximal increases in blood glucose following a 50-g starch meal were 6.09 +/- 0.02 mmol/l with placebo, but 3.17 +/- 0.59 mmol/l (p less than 0.05) with 10 mg and 1.69 +/- 0.41 mmol/l (p less than 0.05) with 30 mg Trestatin . The corresponding insulin increases were: 58.8 +/- 12.7 mU/l, 31.5 +/- 9.7 mU/l (p less than 0.05) and 23.4 +/- 4.8 mU/l (p less than 0.05). Trestatin fully retained this pharmacological activity during treatment for 4 weeks in the diabetic patients. Trestatin did not influence glucose and insulin profiles after oral glucose and sucrose. These results are consistent with a specific inhibition of alpha-amylase in man.