CN-119136820-B - Methods and compositions for stabilizing blood glucose

Abstract

Methods and compositions for lowering blood glucose, reducing blood glucose elevation, and/or lowering the glycemic index of a foodstuff are provided and described herein.

Inventors

• Mai Weixin

Assignees

• 迪杰斯蒂维公司

Dates

Publication Date

20260508

Application Date

20230125

Priority Date

20220126

Claims (11)

1. Use of a S53 family protease in the manufacture of a medicament for reducing blood glucose elevation in a subject after consumption of a composition comprising a legume protein, wherein the legume protein is a pea protein, and wherein the amino acid sequence of the S53 family protease is SEQ ID No. 1.
2. 2. The use of claim 1, wherein the composition further comprises a sugar.
3. 3. The use of claim 1, wherein the composition further comprises fruit.
4. 4. The use of claim 1, wherein the S53 family protease is for administration with the composition.
5. 5. The use of claim 1, wherein the S53 family protease is for administration after the composition.
6. 6. The use of claim 1, wherein the S53 family protease is active in a pH range between pH 2 and pH 5.
7. 7. Use according to claim 1, wherein the pea proteins are derived from peas.
8. 8. The use of claim 1, wherein the increase in blood glucose is reduced relative to consumption of a composition that does not comprise the S53 family protease.
9. 9. The use of claim 1, wherein the medicament is for self-administration by the subject.
10. 10. The use of claim 1, wherein the subject is a mammal.
11. 11. The use of claim 1, wherein the subject is a human.

Description

Methods and compositions for stabilizing blood glucose Cross reference The application claims the benefit of U.S. provisional application No. 63/303,112, filed on 1 month 26 2022, the entire contents of which are hereby incorporated by reference. Background It is well known that high blood glucose has many adverse health effects. Long-term complications of hyperglycemia can range from cardiovascular disease, neuropathy, kidney and blood vessel damage to skeletal and joint problems. The most common method of controlling blood glucose levels is by controlling sugar intake in the diet. While this is a rational and effective strategy, it requires the individual to be very careful in knowing and calculating the amount of carbohydrate ingested per meal. Drugs such as insulin are widely used, however, effective control of blood glucose levels by drugs can present a number of problems. Disclosure of Invention While the biology and etiology of diseases associated with or caused by high blood glucose levels is continually becoming more understood, individuals who cannot regulate blood glucose levels independently of any intervention are still burdened with tremendous burden. For both drug therapies (e.g., insulin hormone) and non-drug therapies (e.g., meal monitoring), both can be considered as substantial interventions with inherent disorders that effectively treat and manage high blood glucose related diseases. Such inherent obstacles include, for example, treatment compliance (e.g., caused by the complexity of treatment), economic burden and access (e.g., self-payment of insured and non-insured individuals), and other factors related to the patient, prescription and prescriber. Such disorders and their impact on the treatment of high blood glucose related diseases place a significant health and economic burden on individuals and healthcare systems. Compositions and methods useful for modulating (e.g., reducing, stabilizing, etc.) high blood glucose are provided and described herein. The methods and compositions provided are based in part on the surprising discovery that high blood glucose regulation can be achieved by providing legume proteins (e.g., pea proteins) and S53 family proteases to an individual. In some embodiments, the S53 family protease Kumamolisin precursor (pro-Kumamolisin). In some embodiments, the S53 protease (e.g., kumamolisin precursor) comprises an amino acid sequence having at least 85% sequence identity to any one of SEQ ID NOs 1 and 3-11. In some embodiments, the S53 protease (e.g., kumamolisin precursor) comprises an amino acid sequence having at least 95% sequence identity to any one of SEQ ID NOs 1 and 3-11. In some embodiments, the S53 protease (e.g., kumamolisin precursor) comprises an amino acid sequence having at least 98% sequence identity to any one of SEQ ID NOs 1 and 3-11. In some embodiments, the active site of the S53 protease comprises amino acid residue E266, F295 or A295, S316, W317, G318, A349, A350 or S350, G351, D352, S353 or D353 or A353 or N353, D367 or E367, G462, G463, T464, S465 and A466 of SEQ ID NO. 1. In some embodiments, the S53 protease is active at a pH of less than about pH 5 (e.g., as measured by protein digestion). In some embodiments, the S53 protease is active at a pH of less than about pH 4.5. In some embodiments, the S53 protease is active at a pH of less than about pH 5. In some embodiments, the S53 protease is active at a pH of less than about pH 4. In some embodiments, the S53 protease is active at a pH of less than about pH 3.5. In some embodiments, the S53 protease is active at a pH of less than about pH 3. In some embodiments, the S53 protease is active over a pH range between about pH 2 and pH 5. In some embodiments, the S53 protease is active over a pH range between about pH 2.5 and pH 4.5. In some embodiments, the S53 protease has at least 50% activity (e.g., relative to its maximum activity) over a pH range between about pH 2.5 and pH 4.5. In certain examples (instance), modulating the pattern of protein digestion (e.g., by administering legume proteins and S53 protease (e.g., kumamolisin precursors)) increases the concentration of certain dietary amino acids in the blood. In such examples, modulating the protein digestion pattern may induce different physiological responses, such as a decrease in blood glucose levels found. In certain examples, digestion of the dietary protein in the gut, for example by administration of legume proteins and S53 protease (e.g., kumamolisin precursor), results in bioactive peptides having potent biological responses, including antidiabetic effects (e.g., lowering blood glucose levels). As described and provided herein, a foodstuff composed of a protein foodstuff (e.g., legume protein) and an acid protease (e.g., kumamolisin precursor) is capable of lowering blood glucose levels (e.g., when consumed with sugar). Furthermore, in certain examples, the addition of a protein food (e.g., legume protein) having an aci