In this research, peptide-based substances that block the breakdown of large sugar matter in the body and lower blood sugar levels will be produced and developed as antidiabetic drugs.
The search for more potent antidiabetic drugs continues as diabetes mellitus, or simply diabetes, continues to affect more people, wrecking health and claiming lives. In the Philippines alone, diabetes affects one in every 25 Filipinos as of 2005, and was the ninth cause of death from 1999 to 2002.
Characterized by elevated blood sugar levels, diabetes can cause cardio-vascular diseases which can eventually lead to death without proper and timely treatments.
There are two types of diabetes mellitus. Type I, characterized by little to no insulin production due to the destruction of the insulin-producing beta cells of the pancreas by the immune system, results in an inability to process sugar from the bloodstream. In type II diabetes, there is production of insulin: however, the cells cannot use it effectively due to abnormalities in both insulin secretion and action. Type II is often the result of poor lifestyle choices, obesity, and sedentary lifestyles. As with most lifestyle-related diseases, diabetes is a chronic and progressive disease.
While insulin injections are typically necessary for diabetes type I patients, antidiabetic drugs that target blood sugar control are more effective for type II diabetes patients. These drugs typically decrease the sugar concentration in the blood by slowing the rate of sugar production and breakdown in the body, r by increasing insulin sensitivity. Four main classes of antidiabetic drugs are available for blood sugar control – sensitizers, secretagogues, incretin analogs, and alpha-glucosidase inhibitors. In this project, antidiabetic drugs of the alpha-glucosidase inhibitors class will be developed.
Alpha-glucosidase inhibitors lower blood sugar levels by blocking the action of the alpha-glucosidase enzymes found in the small intestine. Alpha-glucosidase is an enzyme that breaks down starch and other large sugars into simple forms that could be absorbed from the intestine into the bloodstream. Blocking alpha-glucosidase decreases the rate of sugar breakdown and absorption of sugar from starch. This leads to a decrease in the sugar spike in the blood shortly after food intake. If this matches the slowing of insulin production by the pancreas, then the overall control of blood sugar can be improved. Examples of commercially available antidiabetic drugs that act as alpha-glucosidase inhibitors include acarbose (Precose) and migitol (Glyset).
A number of researchers have focused on the search for more effective inhibitors of antidiabetic compounds from natural materials. Among such compounds are peptides obtained from animals and plants. Peptides are naturally occurring substances that can be described as short chains of amino acids. It can be said that peptides are smaller versions of proteins, since proteins are also biological substances consisting of long chains of amino acids. It can be said that peptides are smaller versions of proteins, since proteins are also biological substances consisting of long chains of amino acids. One can also think of peptides as the product when proteins are broken down into smaller forms.
It has been reported that peptides produced when whey proteins and albumin (a protein found in egg white) are broken down exhibit antidiabetic activity by blocking alpha-glucosidase. Peptides found in silk cocoons produced by Bombyx mori (also known as silkworm) and in the roots of Gypsophila oldhamiana (more commonly known as Manchurian baby’s breath) were also isolated and found to have alpha-glucosidase inhibitory activity.
The search for effective alpha-glucosidase inhibitors has also resulted in findings that small molecules like phthalimides and Schiff bases are potential alpha-glucosidase inhibitors. Small molecules are low molecular weight organic compounds that may regulate biological processes.
In this project, we will merge the natural with the artificial in order to create a much more potent antidiabetic drug. We will produce chemically the natural peptides that have been reported to exhibit alpha-glucosidase inhibition, attach them with the small molecules which are also reported to have alpha-glucosidase activity, and determine the combination which has the most potential as a drug that can be used for the treatment of diabetes.
Written by: Dr. Portia Mahal G. Sabido University of the Philippines Diliman Published by: Department of Science and Technology-Science and Technology Information Institute (DOST-STII)