CN114794487A - A method for treating diabetes - Google Patents

A method for treating diabetes Download PDF

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Publication number
CN114794487A
CN114794487A CN202110089693.6A CN202110089693A CN114794487A CN 114794487 A CN114794487 A CN 114794487A CN 202110089693 A CN202110089693 A CN 202110089693A CN 114794487 A CN114794487 A CN 114794487A
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product
composition
diabetes
another preferred
mammal
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陈雁
韦思颖
王滔
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Shanghai Institute of Nutrition and Health of CAS
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Shanghai Institute of Nutrition and Health of CAS
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/17—Amino acids, peptides or proteins
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D85/00—Containers, packaging elements or packages, specially adapted for particular articles or materials
    • B65D85/62—Containers, packaging elements or packages, specially adapted for particular articles or materials for stacks of articles; for special arrangements of groups of articles
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Abstract

The invention provides a method for treating diabetes, and particularly provides a product, wherein the product contains 2-10 wt% of protein, and the product can effectively treat the diabetes based on the total weight of the product.

Description

A method for treating diabetes
Technical Field
The present invention is in the field of nutrition, and more particularly, the present invention relates to a method of treating diabetes.
Background
Diabetes mellitus is a complex metabolic disease characterized by hyperglycemia, a chronic syndrome caused by the inability of the body to secrete or utilize insulin. Dietary pattern and composition of diet are considered to be one of the most important factors affecting the development of chronic diseases. Meanwhile, diet restriction is an extremely effective dietary pattern for treating a variety of metabolic diseases such as diabetes, obesity, tumor, neovascular disease, etc. In recent years, a group of subjects starts to research a brand-new nutritional intervention means by starting with diet restriction, and finds that the type 1 and type 2 diabetes of mice can be effectively relieved by an intermittent low-protein diet method. However, no accurate conclusion about how much low protein intervention is most obvious is made.
Studies on the effects of modifying protein diets on glycemic control in diabetic patients have not been known so far.
Therefore, there is a strong need in the art to develop an effective, non-side-effect, and low-cost method for treating diabetes.
Disclosure of Invention
The invention aims to provide an effective, side-effect-free and low-cost method for treating diabetes.
In a first aspect of the invention, there is provided a product comprising from 2 to 10 wt%, preferably from 2 to 8 wt%, more preferably from 2.5 to 7.5 wt% protein, based on the total weight of the product.
In another preferred embodiment, the protein is derived from natural food, including any protein supplement that meets national standards.
In another preferred embodiment, the product comprises a composition.
In another preferred embodiment, the composition comprises a food composition, a nutritional composition, a pharmaceutical composition.
In another preferred embodiment, the composition comprises a dietary supplement.
In another preferred embodiment, the product further comprises a normal protein diet.
In another preferred embodiment, the product also comprises other medicines for preventing and/or treating diabetes.
In another preferred embodiment, the other agent for preventing and/or treating diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
In another preferred embodiment, the protein is present in the product in an amount of 1-99 wt%, preferably 10-90 wt%, more preferably 30-70 wt% based on the total weight of the product.
In another preferred embodiment, the other diabetes preventing and/or treating drug in the product is 1-99 wt%, preferably 10-90 wt%, more preferably 30-70 wt% of the total weight of the product.
In another preferred example, in the product, the weight ratio of the protein to the medicament for preventing and/or treating diabetes is 1:100 to 100: 1, preferably 1:10 to 10: 1.
in another preferred embodiment, the other agent for preventing and/or treating diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
In another preferred embodiment, the product may be a single component or a mixture of multiple components.
In another preferred embodiment, the product is used for the prevention and/or treatment of diabetes.
In another preferred embodiment, the product is used for preparing a medicament or preparation for preventing and/or treating diabetes.
In another preferred embodiment, the pharmaceutical dosage form is a non-oral administration dosage form.
In another preferred embodiment, the non-oral administration dosage form is injection or injection.
In another preferred embodiment, the total content of the protein and the agent for preventing and/or treating diabetes is 1 to 99 wt%, and more preferably 5 to 90 wt% of the total weight of the composition.
In another preferred embodiment, the diabetes is selected from the group consisting of: type 1 diabetes, type 2 diabetes, or diabetes caused by other conditions (e.g., gestational diabetes, post-operative diabetes).
In another preferred embodiment, the product is further used for one or more uses selected from the group consisting of:
(a) lowering fasting blood glucose levels in the mammal;
(b) increasing proliferation of islet beta cells in a mammal;
(c) increasing C-Peptide levels in serum of a mammal;
(d) enhancing the insulin-secreting ability of islet beta cells in a mammal;
(e) increasing the sensitivity of liver and skeletal muscle tissues to insulin.
In a second aspect, the invention provides a composition comprising a product according to the first aspect of the invention.
In another preferred embodiment, the composition comprises a food composition, a nutritional composition, a pharmaceutical composition.
In another preferred embodiment, the composition comprises a dietary supplement.
In another preferred embodiment, the composition further comprises a normal protein diet.
In another preferred embodiment, the composition further comprises other drugs for preventing and/or treating diabetes.
In another preferred embodiment, the other agent for preventing and/or treating diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
In another preferred embodiment, the product is present in the composition in an amount of 1 to 99 wt%, preferably 10 to 90 wt%, more preferably 30 to 70 wt%, based on the total weight of the composition.
In another preferred embodiment, the other diabetes preventing and/or treating agent is 1-99 wt%, preferably 10-90 wt%, and more preferably 30-70 wt% of the total weight of the product in the composition.
In another preferred embodiment, in the composition, the weight ratio of the product to the medicament for preventing and/or treating diabetes is 1:100 to 100: 1, preferably 1:10 to 10: 1.
in another preferred embodiment, the other agent for preventing and/or treating diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
In another preferred embodiment, the composition can be a single component or a mixture of a plurality of components.
In another preferred embodiment, the composition is used for preparing a medicament or a preparation for preventing and/or treating diabetes.
In another preferred embodiment, the pharmaceutical dosage form is a non-oral administration dosage form.
In another preferred embodiment, the non-oral administration dosage form is injection or injection.
In a third aspect the invention provides a kit comprising:
(i) a first container, and in the first container, an active ingredient (a1) a product according to the first aspect of the invention or a composition according to the second aspect of the invention, or a medicament containing an active ingredient (a 1); and
(ii) optionally a second container, and an additional agent for the prophylaxis and/or treatment of diabetes for the active ingredient (a2) or an agent containing the active ingredient (a2) in the second container.
In another preferred embodiment, the first container and the second container are the same or different containers.
In another preferred embodiment, the drug of the first container is a single formulation comprising the product of the first aspect of the invention or the composition of the second aspect of the invention.
In another preferred embodiment, the drug in the second container is a single preparation containing other drugs for preventing and/or treating diabetes.
In another preferred embodiment, the dosage form of the drug is an injectable dosage form.
In another preferred embodiment, the kit further comprises instructions describing the prevention and/or treatment of diabetes by administering the active ingredient (a1) in combination with the active ingredient (a 2).
In another preferred embodiment, the formulation comprising the active ingredient (a1) of the product of the first aspect of the invention or the composition of the second aspect of the invention or the formulation comprising the other drug for the prevention and/or treatment of diabetes, respectively, comprises an intravenous injection.
In a fourth aspect, the present invention provides a use of a product according to the first aspect of the present invention or a composition according to the second aspect of the present invention or a kit according to the third aspect of the present invention for the manufacture of a composition or a medicament for the prevention and/or treatment of diabetes.
In another preferred embodiment, the composition comprises a food composition, a nutritional composition, a pharmaceutical composition.
In another preferred embodiment, the composition comprises a dietary supplement.
In another preferred embodiment, the diabetes is selected from the group consisting of: type 1 diabetes, type 2 diabetes, diabetes caused by other conditions (such as gestational diabetes, post-operative diabetes).
In another preferred embodiment, the composition or medicament is further for one or more uses selected from the group consisting of:
(a) lowering fasting blood glucose levels in the mammal;
(b) increasing proliferation of islet beta cells in a mammal;
(c) increasing C-Peptide levels in serum of a mammal;
(d) enhancing the insulin-secreting ability of islet beta cells in a mammal;
(e) increasing the sensitivity of liver and skeletal muscle tissues to insulin.
In another preferred embodiment, the mammal includes a mammal having diabetes.
In another preferred embodiment, the mammal comprises a human or non-human mammal.
In another preferred embodiment, the non-human mammal includes a rodent (e.g., a mouse, rat, or rabbit), a primate (e.g., monkey).
In another preferred embodiment, the pharmaceutical composition comprises (a) the product of claim 1; and (b) a pharmaceutically acceptable carrier.
In another preferred embodiment, the pharmaceutical composition is a liquid, solid, or semi-solid.
In another preferred embodiment, the dosage form of the pharmaceutical composition comprises an injection or an injection.
In another preferred embodiment, in the pharmaceutical composition, the component (a) accounts for 1-99 wt%, preferably 10-90 wt%, and more preferably 30-70 wt% of the total weight of the pharmaceutical composition.
In another preferred embodiment, the pharmaceutical composition further comprises other drugs for preventing and/or treating diabetes.
In another preferred embodiment, the pharmaceutical composition further comprises a normal protein diet.
In another preferred embodiment, the other agent for preventing and/or treating diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
In another preferred embodiment, the composition or medicament can be used alone or in combination in the application of preventing and/or treating diabetes.
In another preferred embodiment, the combination comprises: in combination with other drugs for preventing and/or treating diabetes.
In a fifth aspect, the present invention provides a method for preventing and/or treating diabetes, comprising the steps of:
administering to a subject in need thereof a product according to the first aspect of the invention or a composition according to the second aspect of the invention or a kit according to the third aspect of the invention.
In another preferred embodiment, said administering comprises injecting.
In another preferred embodiment, the subject comprises a human or non-human mammal.
In another preferred embodiment, the non-human mammal includes rodents and primates, preferably mice, rats, rabbits, monkeys.
In another preferred embodiment, the product of claim 1 is administered at a frequency of 1-5 consecutive days per week, preferably 2-4 consecutive days per week, more preferably 3-4 consecutive days per week.
In another preferred embodiment, the product of claim 1 is applied for a period of 2 to 12 weeks, preferably 3 to 12 weeks, more preferably 4 to 12 weeks, more preferably 5 to 12 weeks.
In a sixth aspect, the present invention provides a method of (a) lowering fasting blood glucose levels in a mammal; and/or (b) increasing proliferation of islet beta cells in the mammal; and/or (C) increasing C-Peptide levels in serum of a mammal; and/or (d) enhancing the insulin-secreting ability of islet beta cells of a mammal; and/or (e) a method of increasing the sensitivity of liver and skeletal muscle tissue to insulin comprising:
administering to a subject in need thereof a product according to the first aspect of the invention or a composition according to the second aspect of the invention or a kit according to the third aspect of the invention.
In another preferred embodiment, said administering comprises injecting.
In another preferred embodiment, the subject comprises a human or non-human mammal.
In another preferred embodiment, the subject comprises a human or non-human mammal suffering from diabetes.
In another preferred embodiment, the non-human mammal includes rodents and primates, preferably mice, rats, rabbits, monkeys.
It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be reiterated herein, but to the extent of space.
Drawings
FIG. 1 shows that intermittent low-protein (about 5%) diet can effectively reduce blood glucose level of type I diabetic mice and promote insulin secretion (A, B: schematic diagram of diet intervention mode of mice; C: change of fasting blood glucose of each group of mice under intermittent different concentrations of protein diet, area under curve is shown on the right side; D: proliferation condition of islet beta cells after different concentrations of protein intervention; E: change of concentration of C-Peptide in serum of different groups of mice represents P value <0.05, <0.01, < P value, and <0.001, and ns represents non-significant difference.
Detailed Description
As a result of extensive and intensive studies, the present inventors have for the first time unexpectedly found that a dietary regimen with a specific concentration of a protein is effective in treating diabetes, and that a dietary regimen with a specific concentration of a protein also (a) reduces fasting blood glucose levels in a mammal; and/or (b) increasing proliferation of islet beta cells in the mammal; and/or (C) increasing C-Peptide levels in serum of a mammal; and/or (d) enhancing the insulin-secreting ability of islet beta cells of a mammal; and/or (e) increasing the sensitivity of liver and skeletal muscle tissue to insulin. The method has no side effect and low cost. On this basis, the present inventors have completed the present invention.
Normal protein diet
In the invention, the index finger of a normal protein meal has a normal recommended amount (the recommended amount of protein per day of a human body is 60 g).
Dietary supplement
The present invention also provides a dietary supplement for the alleviation or treatment of diabetes comprising 2-10%, preferably 2-8%, more preferably 2.5-7.5% (wt%) protein based on the total weight of the product.
Herein, in the present invention, the source of the protein is not particularly limited, and the protein may be derived from natural food, including any protein supplement that meets the national standard.
Diabetes mellitus
Diabetes mellitus is a complex metabolic disease characterized by hyperglycemia, a chronic syndrome caused by the inability of the body to secrete or utilize insulin.
In particular, Diabetes Mellitus (DM) is a group of systemic metabolic diseases characterized by chronic hyperglycemia due to a deficiency in insulin secretion or action caused by multiple etiologies. Long-term sugar, fat and protein metabolism disorder can cause multiple organ damage and homeostatic imbalance, and can cause chronic pathological changes, hypofunction, even failure and other complications of tissues and organs such as heart, kidney, eye, nerve, blood vessel and the like. Type 1 diabetes (diabetes mellitus type 1, T1DM) and type 2 diabetes (diabetes mellitus type 2, T2DM) are two important subtypes of diabetes, and the pathogenesis of both is different. The continuous rise of blood sugar is a key factor of multiple organ injury caused by diabetes, so that the effect of reducing the blood sugar-caused organ injury while treating by using insulin to reduce the blood sugar is a significant scientific problem.
The invention starts with diet restriction, researches a brand new nutritional intervention means, and particularly importantly, discovers that a diet scheme of specific concentration protein can effectively treat diabetes, and can also (a) reduce the fasting blood glucose level of mammals by using the diet scheme of specific concentration protein; and/or (b) increasing proliferation of islet beta cells in the mammal; and/or (C) increasing C-Peptide levels in serum of a mammal; and/or (d) enhancing the ability of a mammalian islet beta cell to secrete insulin, and/or (e) increasing the sensitivity of liver and skeletal muscle tissue to insulin.
Pharmaceutical compositions and methods of administration
In another aspect, the invention provides a pharmaceutical composition comprising (a) a safe and effective amount of a product according to the first aspect of the invention or a composition according to the second aspect of the invention; and (b) a pharmaceutically acceptable carrier or excipient. The dose of the component (a) of the present invention is usually 10. mu.g to 100 mg per dose, preferably 100. mu.g to 1000. mu.g per dose. For the purposes of the present invention, an effective dose is about 0.01 mg/kg to 50mg/kg, preferably 0.05 mg/kg to 10 mg/kg of body weight of the product of the invention to be administered to a subject. In addition, component (a) of the present invention may be used alone or in combination (e.g., formulated in the same pharmaceutical composition) with other therapeutic agents (e.g., other agents for the prevention and/or treatment of diabetes).
The pharmaceutical composition may further comprise a pharmaceutically acceptable carrier. The term "pharmaceutically acceptable carrier" refers to a carrier for administration of a therapeutic agent. The term refers to such pharmaceutical carriers: they do not themselves induce the production of antibodies harmful to the individual receiving the composition and are not unduly toxic after administration. Such vectors are well known to those of ordinary skill in the art. A thorough discussion of pharmaceutically acceptable excipients can be found in Remington's Pharmaceutical Sciences (Mack pub. co., n.j.1991). Such vectors include (but are not limited to): saline, buffer, glucose, water, glycerol, ethanol, adjuvants, and combinations thereof.
Pharmaceutically acceptable carriers in therapeutic compositions can comprise liquids such as water, saline, glycerol and ethanol. In addition, auxiliary substances, such as wetting or emulsifying agents, pH buffering substances and the like may also be present in these carriers.
Generally, the therapeutic compositions can be prepared as injectables, e.g., as liquid solutions or suspensions; solid forms suitable for constitution with a solution or suspension, or liquid carrier, before injection, may also be prepared.
Once formulated, the compositions of the present invention may be administered by conventional routes including, but not limited to: intratumoral, intramuscular, intravenous, subcutaneous, intradermal, or topical administration. The subject to be prevented or treated may be an animal; especially a human.
When the pharmaceutical composition of the present invention is used for practical treatment, various dosage forms of the pharmaceutical composition may be used depending on the use case. Preferably, the injection is intravenous injection or intratumoral injection.
These pharmaceutical compositions may be formulated by mixing, dilution or dissolution according to a conventional method, and occasionally, suitable pharmaceutical additives such as excipients, disintegrants, binders, lubricants, diluents, buffers, isotonic agents (isotonicities), preservatives, wetting agents, emulsifiers, dispersants, stabilizers and solubilizing agents are added, and the formulation process may be carried out in a conventional manner according to the dosage form.
For example, ophthalmic eye drops can be formulated by: the product of the present invention is dissolved in sterile water (in which a surfactant is dissolved) together with a basic substance, the osmotic pressure and the pH value are adjusted to physiological states, and suitable pharmaceutical additives such as preservatives, stabilizers, buffers, isotonic agents, antioxidants and viscosity increasing agents may be optionally added and then completely dissolved.
The pharmaceutical compositions of the present invention may also be administered in the form of sustained release formulations. For example, component (a) of the present invention may be incorporated into a pellet or microcapsule in which a sustained-release polymer is used as a carrier, and then the pellet or microcapsule is surgically implanted into the tissue to be treated. As examples of the sustained-release polymer, ethylene-vinyl acetate copolymer, polyhydroxymethacrylate, polyacrylamide, polyvinylpyrrolidone, methylcellulose, lactic acid polymer, lactic acid-glycolic acid copolymer and the like can be exemplified, and biodegradable polymers such as lactic acid polymer and lactic acid-glycolic acid copolymer can be preferably exemplified.
When the pharmaceutical composition of the present invention is used for practical treatment, the dose of the component (a) of the present invention as an active ingredient can be determined reasonably according to the body weight, age, sex, and degree of symptoms of each patient to be treated.
The main advantages of the invention include:
(1) the present invention has for the first time discovered that a dietary regimen of a specific concentration of a protein is effective in treating diabetes, and that a dietary regimen using a specific concentration of a protein also (a) reduces fasting blood glucose levels in a mammal; and/or (b) increasing proliferation of islet beta cells in the mammal; and/or (C) increasing C-Peptide levels in serum of a mammal; and/or (d) enhancing the insulin-secreting ability of islet beta cells of a mammal; and/or (e) increasing the sensitivity of liver and skeletal muscle tissue to insulin.
(2) Compared with a control group, the invention discovers for the first time that the feed with the protein concentration of 2.5-7.5% can achieve the best effect of reducing the blood sugar of mice by intermittently feeding, and the effect of promoting the proliferation of islet beta cells and the insulin secretion is also most obvious. Therefore, intermittent eating of the diet containing 2.5 to 7.5 percent of protein is expected to become a brand new method for intervening diabetes.
The invention will be further illustrated with reference to the following specific examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. The experimental procedures, for which specific conditions are not noted in the following examples, are generally performed according to conventional conditions such as those described in J. SammBruk et al, molecular cloning guidelines, scientific Press,2002 (New York: Cold Spring Harbor Laboratory Press,2002), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are percentages and parts by weight.
The materials and reagents used in the examples were all commercially available products unless otherwise specified.
The material and the method are as follows:
1.1 materials: male C57BL/6 mice at 8 weeks of age and db/db mice were purchased from Schlay laboratory animals, Inc.; STZ was purchased from Sigma; the EdU kit is purchased from Shanghai Bin Yuntian biotechnology Co., Ltd; the mouse C-Peptide Elisa kit was purchased from Crystal Chem Inc.
1.2 methods
1.2.1STZ constructs a type I diabetes model: the C57 mice with 5h fasting state are injected with STZ (40mg/kg body weight) continuously for 5 days, the blood sugar of the mice is observed to rise remarkably after one week, and the molding is successful;
1.2.2 mouse EdU cell proliferation assay: mice were injected with 50mg/kg of EdU 6 hours prior to sacrifice. After sacrifice, pancreas tissue was fixed and paraffin sections were prepared. Following deparaffinization, rehydration, antigen retrieval of the sections, and staining of the cells with insulin. Cell proliferation was by Beyoclick provided by Biyuntian Biotechnology Ltd TM EdU Cell Proliferation Kit for staining.
1.2.3 detection of serum C-Peptide concentration in mice: after sacrifice, blood was collected and serum was centrifuged and the serum C-Peptide concentration was measured by mouse C-Peptide Elisa kit purchased from Crystal Chem inc.
1.2.3 protocol:
experiment one: a total of 35 male C57BL/6 mice at 8 weeks of age were divided into seven groups of 5 mice each. The first group of mice freely eat common grains every day; the second to the seventh groups of mice respectively eat the protein grains (0 to 20 percent) with different concentrations 3 days before each week and eat the common grains 4 days after each week; repeated weekly for 5 weeks.
1.3 rat food formula
1.3.1 protein rat food formula with different concentrations: protein feeds at different concentrations were purchased from shanghai sailpoise biotechnology limited. The main nutrient components comprise casein, corn starch, sucrose, maltodextrin, cellulose, soybean oil, vitamin mineral mixture and the like.
1.3.2 Normal rat grain formula: normal rat food at 26.5% protein was purchased from shanghai pluripotene biotechnology limited. The main nutrient components comprise fish meal, wheat, corn, bran, vitamins, minerals, amino acids and the like.
Example 1 intermittent Low protein (about 5%) diet is effective in lowering blood glucose levels and promoting insulin secretion in type 1 diabetic mice
The type i diabetes model was first constructed in 8 week old C57 male mice: after 5 consecutive days, STZ (40mg/kg body weight) was injected 5h in the morning after fasting, and a significant rise in blood glucose was observed in the mice one week later, which proved successful molding. Mice in the control group freely eat common grains every day; mice in the second to seventh groups were fed different concentrations of protein (0% -20%) food 3 days before each week and normal food 4 days after each week (fig. 1A, B). The fasting blood glucose levels of mice gradually decreased with protein concentration changes from 0% to 5% under continuous 5 weeks of nutritional intervention, but the effect of blood glucose reduction gradually disappeared when protein concentration was changed from 5% to 20% (fig. 1C). We sacrificed STZ-modeled type one diabetic mice after 5 consecutive weeks of diet, sectioned and EdU (reflecting the level of cell proliferation) stained mouse pancreatic tissue, and statistics showed that proliferation of mouse islet β cells increased significantly with changes in protein concentration from 0% -5%, but gradually disappeared when the protein concentration was changed from 5% to 20% (fig. 1D). Furthermore, we collected mouse serum and tested the level of C-Peptide in the blood circulation of mice (reflecting the insulin secretion ability of islet beta cells) by ELISA (enzyme-linked immunosorbent assay), and found that after 5 weeks of diet dry prognosis, the level of C-Peptide in mouse serum gradually increased with increasing protein concentration from 0% to 5%, but gradually decreased with increasing protein concentration from 5% to 20% (FIG. 1E). Therefore, the optimal concentration of dry pre-diabetes in an intermittent low protein diet is between 2.5% and 7.5%, with 5% being the best.
All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims (10)

1. A product comprising from 2 to 10 wt% protein, based on the total weight of the product.
2. The product of claim 1, wherein the product further comprises a normal protein diet.
3. The product of claim 1, wherein the product further comprises other agents for the prevention and/or treatment of diabetes.
4. The product according to claim 3, wherein the other prophylactic and/or therapeutic agent for diabetes is selected from the group consisting of: metformin, an alpha glucosidase inhibitor, an insulin secretagogue, a dipeptidyl peptidase IV (DPP4) inhibitor, a Thiazolidinedione (TZD), a sodium-glucose cotransporter 2(SGLT2) inhibitor, insulin, a glucagon-like peptide 1(GLP1) receptor agonist, or a combination thereof.
5. A composition comprising the product of claim 1.
6. The composition of claim 5, wherein the composition further comprises a normal protein diet.
7. The composition of claim 5, wherein the composition further comprises other agents for the prevention and/or treatment of diabetes.
8. A kit, comprising:
(i) a first container, and in the first container, an active ingredient (a1) a product of claim 1 or a composition of claim 5, or a medicament containing an active ingredient (a 1); and
(ii) optionally a second container, and an additional agent for the prophylaxis and/or treatment of diabetes for the active ingredient (a2) or an agent containing the active ingredient (a2) in the second container.
9. Use of a product according to claim 1 or a composition according to claim 5 or a kit according to claim 8 for the preparation of a composition or a medicament for the prophylaxis and/or treatment of diabetes.
10. The use of claim 9, wherein the composition or medicament is further for one or more uses selected from the group consisting of:
(a) lowering fasting blood glucose levels in the mammal;
(b) increasing proliferation of islet beta cells in a mammal;
(c) increasing C-Peptide levels in serum of a mammal;
(d) enhancing the insulin-secreting ability of islet beta cells in a mammal;
(e) increasing the sensitivity of liver and skeletal muscle tissues to insulin.
CN202110089693.6A 2021-01-22 2021-01-22 A method for treating diabetes Pending CN114794487A (en)

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CN1431016A (en) * 2003-01-13 2003-07-23 浙江大学 Compositions of health care food for regulating blood sugar and fat as well as its preparing method
CN101175416A (en) * 2005-04-06 2008-05-07 诺瓦提斯公司 A method and composition for nutritionally improving glucose control and insulin action
WO2008066308A1 (en) * 2006-11-30 2008-06-05 Amorepacific Corporation Food composition for increasing the satiety and satiation
WO2008119957A1 (en) * 2007-04-03 2008-10-09 Mars, Incorporated Snack food
CN105231462A (en) * 2015-11-19 2016-01-13 刘庆华 Compound blood-glucose-reducing nutrition powder
CN105744845A (en) * 2013-11-29 2016-07-06 雀巢产品技术援助有限公司 Nutritional compositions with phospholipids
WO2018016675A1 (en) * 2016-07-22 2018-01-25 (주)씨알푸드 Functional cereal bar for inhibiting rise in blood glucose level and manufacturing method therefor
CN108403952A (en) * 2018-05-30 2018-08-17 苏州市李良济健康产业有限公司 It is a kind of to be used to treat Chinese medicinal capsule of type II diabetes and preparation method thereof
CN111406941A (en) * 2020-04-28 2020-07-14 深圳市瑞辰健康管理有限公司 Nutritional dietary compositions and edible products

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1431016A (en) * 2003-01-13 2003-07-23 浙江大学 Compositions of health care food for regulating blood sugar and fat as well as its preparing method
CN101175416A (en) * 2005-04-06 2008-05-07 诺瓦提斯公司 A method and composition for nutritionally improving glucose control and insulin action
WO2008066308A1 (en) * 2006-11-30 2008-06-05 Amorepacific Corporation Food composition for increasing the satiety and satiation
WO2008119957A1 (en) * 2007-04-03 2008-10-09 Mars, Incorporated Snack food
CN105744845A (en) * 2013-11-29 2016-07-06 雀巢产品技术援助有限公司 Nutritional compositions with phospholipids
CN105231462A (en) * 2015-11-19 2016-01-13 刘庆华 Compound blood-glucose-reducing nutrition powder
WO2018016675A1 (en) * 2016-07-22 2018-01-25 (주)씨알푸드 Functional cereal bar for inhibiting rise in blood glucose level and manufacturing method therefor
CN108403952A (en) * 2018-05-30 2018-08-17 苏州市李良济健康产业有限公司 It is a kind of to be used to treat Chinese medicinal capsule of type II diabetes and preparation method thereof
CN111406941A (en) * 2020-04-28 2020-07-14 深圳市瑞辰健康管理有限公司 Nutritional dietary compositions and edible products

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