Control of postprandial hyperglycemia by oral administration of the sea anemone mucus-derived α-amylase inhibitor (magnificamide)

Diabetes mellitus is a serious threat to human health in both developed and developing countries. Optimal disease control requires the use of a diet and a combination of several medications, including oral hypoglycemic agents such as alpha-glucosidase inhibitors. Currently, the arsenal of available drugs is insufficient, which determines the relevance of studying new potent alpha-amylase inhibitors. We implemented the recombinant production of sea anemone derived alpha-amylase inhibitor magnificamide in Escherichia coli. Peptide was isolated by a combination of liquid chromatography techniques. Its folding and molecular weight was proved by H-1 NMR and mass spectrometry. The K-i value of magnificamide against human pancreatic alpha-amylase is 3.1 nM according to Morrison equation for tight binding inhibitors. Our study of the thermodynamic characteristics of binding of magnificamide to human salivary and pancreatic alpha-amylases by isothermal titration calorimetry showed the presence of different binding mechanisms with Kd equal to 0.11 mu M and 0.1 nM, respectively. Experiments in mice with streptozotocin-induced diabetes mimicking diabetes mellitus type 1 were used to study the efficiency of magnificamide against postprandial hyperglycemia. It was found that at a dose of 0.005 mg kg(-1), magnificamide effectively blocks starch breakdown and prevents the development of postprandial hyperglycemia in T1D mice. Our results demonstrated the therapeutic potential of magnificamide for the control of postprandial hyperglycemia.

Automated summary

Diabetes mellitus poses a serious threat to human health worldwide. The current lack of sufficient drugs for diabetes treatment has led to the study of new potent alpha-amylase inhibitors. In this study, we successfully produced the sea anemone derived alpha-amylase inhibitor magnificamide in Escherichia coli. Our results showed that magnificamide effectively inhibits human pancreatic alpha-amylase, and has the potential to control postprandial hyperglycemia.