CN113711994A - Method for establishing cynomolgus monkey type 2 diabetes mellitus model and application thereof - Google Patents
Method for establishing cynomolgus monkey type 2 diabetes mellitus model and application thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K67/00—Rearing or breeding animals, not otherwise provided for; New or modified breeds of animals
- A01K67/02—Breeding vertebrates
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- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23K—FODDER
- A23K50/00—Feeding-stuffs specially adapted for particular animals
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2227/00—Animals characterised by species
- A01K2227/10—Mammal
- A01K2227/106—Primate
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- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01K—ANIMAL HUSBANDRY; AVICULTURE; APICULTURE; PISCICULTURE; FISHING; REARING OR BREEDING ANIMALS, NOT OTHERWISE PROVIDED FOR; NEW BREEDS OF ANIMALS
- A01K2267/00—Animals characterised by purpose
- A01K2267/03—Animal model, e.g. for test or diseases
- A01K2267/035—Animal model for multifactorial diseases
- A01K2267/0362—Animal model for lipid/glucose metabolism, e.g. obesity, type-2 diabetes
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Abstract
The invention relates to the technical field of experimental animal disease models of non-human primates, and discloses a method for establishing a cynomolgus monkey type 2 diabetes model and application thereof. The method comprises the following steps: (1) selecting male cynomolgus monkeys with age of 12-21 years old; (2) feeding the chicken with sugar-containing feed for the first time, feeding the chicken with complementary food for the second time, feeding the chicken with green fodder for the third time, and feeding the chicken with sugar-containing feed for the fourth time; (3) after feeding for one year according to the mode of the step (2), detecting corresponding indexes, and screening out the cynomolgus monkeys with fasting blood sugar level more than 7 mmol/L; wherein the complementary food is fed by alternately feeding the red sugar blocks and the biscuits every three days; the sugar-containing feed is obtained by mixing conventional feed and brown sugar. The method adopts warm feeding mode, establishes cynomolgus monkey type 2 diabetes model, and can be used for drug effect evaluation in new drug research and development process.
Description
Technical Field
The invention relates to the technical field of experimental animal disease models of non-human primates, in particular to a method for establishing a cynomolgus monkey type 2 diabetes model and application thereof.
Background
Diabetes is a metabolic disease characterized by hyperglycemia. Chronic hyperglycemia can lead to chronic damage to, and dysfunction of, various tissues, particularly the eye, kidney, heart, blood vessels, and nerves. Acute severe metabolic disorders, such as diabetic ketoacidosis, hyperosmolar hyperglycemia syndrome, can occur when the condition is severe or under stress. More than 90% of the diseases in China are type 2 diabetes. Type 2 diabetes is a metabolic disease resulting from a combination of insulin secretion defects in islet beta cells and insulin response failure in insulin-sensitive tissues (e.g., skeletal muscle, cardiac muscle, and adipose tissue). According to the international union for diabetes (IDF) data, about 420 people die from diabetes in 2019 globally, 4.63 hundred million 20-79 years old adults suffer from diabetes, and the number of patients is predicted to rise to 7 hundred million in 2045 years. Along with the accelerating urbanization process of China in recent 30 years, the aging of the population is intensified, the prevalence rate of overweight and obesity is increased, and the prevalence rate of diabetes is obviously increased. Epidemiological investigation of thyroid, iodine nutrition status and diabetes by the endocrinology division of the Chinese medical society in 31 provinces of China in 2015 to 2017 shows that the prevalence rate of diabetes in people 18 years old and older in our country is 11.2%, and the total number of diabetic patients is about 1.298 hundred million (7040 million for men and 5940 million for women) and has become the first major country of adult diabetes over India. Diabetes and its complications account for approximately 130 million deaths each year. The annual chinese medical cost for the diabetes field is $ 510 billion in the second world, second only to $ 3200 billion in the united states, and the chinese direct medical costs for diabetes have accounted for 13% of the chinese medical costs. Therefore, research on the treatment of type 2 diabetes is a continuous hot spot of various large medical companies at home and abroad.
In the past, countless scientific research teams aim at constructing an ideal type 2 diabetes animal model and strive to find a new drug for research and development by maximally reproducing the pathological and metabolic characteristics of type 2 diabetes patients. Rodents are ideal vectors for human disease models due to their advantages of small size, short breeding cycle, low cost, ready availability, etc. Rodent models of obesity and diabetes can be obtained by transgenesis, gene knockout, and tissue-specific gene knockout. However, such models do not adequately represent all of the pathophysiological characteristics of type 2 diabetic patients. A rodent diabetes model constructed by combining high-fat diet and low-dose Streptozotocin (STZ) injection shows the pathological characteristics of insulin resistance, and simultaneously, blood sugar, urine volume, urine sugar and urine ketone can show the symptoms of diabetes. Such models are widely used in the study of the pathogenesis and treatment of type 2 diabetes. However, the pathological features of rodents and type 2 diabetics vary greatly in carbohydrate metabolism, islet morphology and function, and blood brain barrier permeability. Rodents do not develop spontaneous type 2 diabetes or hypertensive disorders. While most lines do not develop diet-induced symptoms of type 2 diabetes.
Non-human primates, when they suffer from metabolic syndrome, show central symptoms of centripetal obesity, insulin resistance, dyslipidemia and hypertension, which are very similar to those of humans. Non-human primates can spontaneously develop type 2 diabetes with aging and ingestion of a high calorie diet. Through the controllable longitudinal research on the non-human primates, the pathological changes in the development process of the type 2 diabetes mellitus can be observed. Non-human primate models currently commonly used for type 2 diabetes research include high fructose diet-induced models, high fat diet-induced models, and model of aging spontaneous type 2 diabetes. High fructose and high fat diets induce non-human primates to develop symptoms of central obesity, dyslipidemia and insulin resistance, and in part, typical type 2 diabetes. In the high fructose diet induction construction, the role of fructose is unknown. Reports have shown that non-human primates do not show obesity and metabolic syndrome, but show markers of impaired liver function, on the premise of controlling caloric intake. The high fat diet induction model can be used for drug effect research of obesity, metabolic syndrome and type 2 diabetes. The model has particular effect on inhibiting the detection of feeding-type drugs. However, non-human primates dislike high fat diet and are prone to diarrhea, rectocele, and other diseases. Moreover, the high saturated fat and high cholesterol diet inhibits endogenous cholesterol synthesis, limiting the model application. The model of type 2 diabetes, which is spontaneous in aging, is limited in its use due to its long cycle and high cost. Recently, non-human primates have been applied to the study of the safety and efficacy of type 2 diabetes drugs. The results obtained in the non-human primate type 2 diabetes model were consistent with clinical studies in pharmacological studies of FGF-21 analogs, MC4R agonists, and GLP-1R treatment.
In summary, the non-human primate model has more important value in the development of new drugs for type 2 diabetes than rodents.
Disclosure of Invention
Currently, the main approach for establishing animal models of type 2 diabetes is by feeding a high fructose high fat diet in combination with Streptozotocin (STZ) injection. The animal model obtained by the method does not conform to the real pathogenesis of the type 2 diabetes and does not simulate the chronic pathogenesis of the type 2 diabetes; worse, STZ injection can cause severe chemical injury to animals (especially non-human primates) due to dislike of high fat diet and easy occurrence of diarrhea and proctoptosis, thus resulting in low success rate and high mortality rate of animals. Therefore, the invention aims to provide a method for establishing a cynomolgus monkey type 2 diabetes model by feeding mild feed without chemical intervention and application thereof.
In order to achieve the above object, the present invention provides a method for establishing a cynomolgus monkey type 2 diabetes mellitus complicated myocardial injury model, comprising the following steps:
(1) selecting male cynomolgus monkeys with age of 12-21 years old;
(2) feeding the chicken with sugar-containing feed for the first time, feeding the chicken with complementary food for the second time, feeding the chicken with green fodder for the third time, and feeding the chicken with sugar-containing feed for the fourth time;
(3) after feeding for one year according to the mode of the step (2), detecting corresponding indexes, and screening out the cynomolgus monkeys with fasting blood sugar level more than 7 mmol/L;
wherein the complementary food is fed by alternately feeding the red sugar blocks and the biscuits every three days;
the sugar-containing feed is obtained by mixing conventional feed and brown sugar.
Preferably, the content of brown sugar in the sugar-containing feed is 10-15 wt%.
Preferably, the ingredients of the conventional feed comprise corn, soybean meal and fish meal.
Preferably, the ingredients of the brown sugar piece comprise white granulated sugar, brown granulated sugar and water;
preferably, the ingredients of the biscuit comprise wheat flour, cream, white granulated sugar, shredded coconut, edible salt, glucose, ammonium bicarbonate and flavourings.
Preferably, the first feeding of the sugar-containing feed is carried out with a feeding weight of 120 g;
preferably, the first feeding of the sugar-containing feed is carried out for a period of 7: 30-8: 00.
preferably, in the complementary food feeding, the feeding weight of the red sugar block is 30 g when the red sugar block is fed, and the feeding weight of the biscuit is 25 g when the biscuit is fed;
preferably, the time for feeding the supplementary material for the second time is 12: 00-12: 30.
preferably, the feeding weight of the third feeding green fodder is 100 g;
preferably, the time for feeding the green fodder for the third time is 14: 00-14: 30.
preferably, the fourth feeding of the sugar-containing feed has a feeding weight of 120 g;
preferably, the fourth feeding of the sugar-containing feed is carried out for a time of 17: 00-17: 30.
the second aspect of the invention provides an application of the establishing method of the cynomolgus monkey type 2 diabetes mellitus model in diabetes treatment.
Preferably, the cynomolgus monkey type 2 diabetes model constructed by the method is used for discovering a therapeutic drug for type 2 diabetes.
The invention adopts mild long-term high-sugar and high-fat feeding, establishes a type 2 diabetes cynomolgus monkey model, and can be used for evaluating the drug effect in the process of developing new drugs. The rodent type 2 diabetes model is mainly replicated by feeding high fructose high fat diet combined with STZ injection, but the model has low success rate and high death rate, and does not accord with the pathogenesis of human type 2 diabetes. Compared with the cynomolgus monkey type 2 diabetes mellitus model established by the invention, the cynomolgus monkey type 2 diabetes mellitus model has the main advantages that:
1. in the feeding scheme used by the invention, the feed has very low fat addition amount, does not contain cholesterol, does not contain chemical medicine injection, and avoids the serious defects caused by high fat feeding and STZ injection.
2. The model established by the invention is a cynomolgus monkey model, the genetic background and the physiological structure of the cynomolgus monkey have high homology with human, the cynomolgus monkey model can spontaneously develop type 2 diabetes, and the symptoms are highly similar to the symptoms of the human.
3. The invention adopts the long-term mild sugar-containing feed, the brown sugar blocks and the biscuits for feeding to replace the traditional high-fat high-fructose feeding, thereby avoiding the damage effect of the fructose on the liver after long-term feeding and the phenomena of diarrhea and rectocele caused by the traditional high-fat feeding.
Drawings
FIG. 1 is a graph showing the results of comparison of finger blood glucose level, peripheral blood glucose level, c-peptide level in blood, insulin level and glycated hemoglobin level between the model group and the control group.
Detailed Description
The following detailed description of embodiments of the invention refers to the accompanying drawings. It should be understood that the detailed description and specific examples, while indicating the present invention, are given by way of illustration and explanation only, not limitation.
The endpoints of the ranges and any values disclosed herein are not limited to the precise range or value, and such ranges or values should be understood to encompass values close to those ranges or values. For ranges of values, between the endpoints of each of the ranges and the individual points, and between the individual points may be combined with each other to give one or more new ranges of values, and these ranges of values should be considered as specifically disclosed herein.
The invention provides a method for establishing a cynomolgus monkey type 2 diabetes mellitus combined myocardial injury model, which comprises the following steps:
(1) selecting male cynomolgus monkeys with age of 12-21 years old;
(2) feeding the chicken with sugar-containing feed for the first time, feeding the chicken with complementary food for the second time, feeding the chicken with green fodder for the third time, and feeding the chicken with sugar-containing feed for the fourth time;
(3) after feeding for one year according to the mode of the step (2), detecting corresponding indexes, and screening out the cynomolgus monkeys with fasting blood sugar level more than 7 mmol/L;
wherein the complementary food is fed by alternately feeding the red sugar blocks and the biscuits every three days;
the sugar-containing feed is obtained by mixing conventional feed and brown sugar.
In a preferred embodiment, the sugar-containing feed contains brown sugar in an amount of 10 to 15 wt%. Specifically, the content of brown sugar in the sugar-containing feed may be 10 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, or 15 wt%.
In a preferred embodiment, the ingredients of the conventional feed comprise corn, soybean meal and fish meal.
Further preferably, the nutrient composition of the sugar-containing feed is as shown in table 1.
In the invention, the NRV% value in the nutrient component table is calculated by reference to GB 28050-2011.
TABLE 1
| Item | Each 100g |
| (Energy) | ≥1590kj |
| Protein | 15-20g |
| Fat | 5-7g |
| Cholesterol | 0mg |
| Carbohydrate compound | 70-80g |
| Sodium salt | 260-300mg |
In a preferred embodiment, the ingredients of the red sugar block comprise white granulated sugar, brown granulated sugar and water.
In a preferred embodiment, the nutritional composition of the confection is as shown in table 2.
TABLE 2
| Item | Each 100g |
| (Energy) | ≥380kj |
| Protein | 0.5-1.5g |
| Fat | 0g |
| Cholesterol | 0mg |
| Carbohydrate compound | 90-110g |
| Sodium salt | 15-25mg |
In a preferred embodiment, the ingredients of the biscuit comprise wheat flour, cream, white granulated sugar, shredded coconut, edible salt, glucose, ammonium bicarbonate and flavourings.
In a preferred embodiment, the nutritional composition of the biscuit is as shown in table 3.
TABLE 3
| Item | Each 100g |
| (Energy) | ≥1890kj |
| Protein | 3-8g |
| Fat | 15-25g |
| Cholesterol | 0mg |
| Trans fatty acids | 0.5-1.5mg |
| Carbohydrate compound | 50-70g |
| Sodium salt | 250-270mg |
In a preferred embodiment, the first feeding of the sugar-containing feed has a feeding weight of 120 g.
In a preferred embodiment, the first feeding of the sugar-containing feed is carried out for a period of 7: 30-8: 00.
in a preferred embodiment, the feeding weight is 30 grams when feeding the candy bar and 25 grams when feeding the biscuit in a complementary diet.
In a preferred embodiment, the second feeding of the supplementary material is carried out for a period of 12: 00-12: 30.
in a preferred embodiment, the weight of the third feeding of the silage is 100 g.
In a preferred embodiment, the period of feeding the green fodder for the third time is 14: 00-14: 30.
in a preferred embodiment, the fourth feeding of the sugar-containing feed has a feeding weight of 120 g.
In a preferred embodiment, the fourth feeding of the sugar-containing feed is carried out for a time of 17: 00-17: 30.
in the method, a cynomolgus monkey type 2 diabetes model is established by adopting a long-term mild feeding mode. The characteristics of mild feeding include: the feed has low content of sugar and fat, and no fructose and cholesterol. On the premise of ensuring that a cynomolgus monkey type 2 diabetes mellitus model can be successfully obtained through mild feeding, the hidden danger caused by the traditional high-fructose and high-fat (especially high-cholesterol) feeding mode can be avoided.
The second aspect of the invention provides an application of the establishing method of the cynomolgus monkey type 2 diabetes mellitus model in diabetes treatment.
Preferably, the cynomolgus monkey type 2 diabetes model constructed by the method is used for discovering a therapeutic drug for type 2 diabetes.
The invention is further illustrated by the following examples, which are not intended to be limiting.
Example 1
(1) Selecting 31 male cynomolgus monkeys with the age of 12-21 years old; wherein, the cynomolgus monkeys are all from the Tianqin biological science and technology limited company in Hubei, the purchasing procedure meets the requirements of the law regulations of the people's republic of China, and the cynomolgus monkeys are approved by the provincial hall in Hubei and the provincial hall in Guangdong. The experimental monkeys pass physical examination, and all indexes meet the local inspection and quarantine standard.
(2) Feeding the cynomolgus monkey in the step (1) four times a day, 7: 30-8: 00 first feeding of 120 g of sugar-containing feed, 12: 00-12: 30 g of complementary food brown sugar blocks or 25 g of biscuits are fed for the second time, the brown sugar blocks and the biscuits are alternately fed every three days, and the ratio of the total weight of the feed is 14: 00-14: 30 and a third feeding of 100g of green fodder, 17: 00-17: feeding 120 g of sugar-containing feed 30 fourth time, wherein the sugar-containing feed is obtained by mixing conventional feed and red granulated sugar, the content of the red granulated sugar in the sugar-containing feed is 15 wt%, the conventional feed comprises corn, soybean meal and fish meal, and the nutritional ingredients of the sugar-containing feed are shown in Table 4; the components of the brown sugar block comprise white granulated sugar, brown granulated sugar and water, and the nutritional ingredients of the brown sugar block are shown in table 5; the components of the biscuit comprise wheat flour, cream, white granulated sugar, shredded coconut, edible salt, glucose, ammonium bicarbonate and edible spice, and the nutritional ingredients of the biscuit are shown in Table 6.
(3) And (3) feeding the macaca fascicularis for 1 year according to the mode in the step (2), detecting corresponding indexes, and screening the macaca fascicularis with fasting blood glucose level more than 7mmol/L, namely the type 2 diabetes mellitus macaca fascicularis model.
TABLE 4
TABLE 5
| Item | Each 100g |
| (Energy) | 389kj |
| Protein | 0.7g |
| Fat | 0g |
| Cholesterol | 0mg |
| Carbohydrate compound | 100g |
| Sodium salt | 18.3mg |
TABLE 6
| Item | Each 100g |
| (Energy) | 1898kj |
| Protein | 5.3g |
| Fat | 20g |
| Cholesterol | 0mg |
| Trans fatty acids | 0.9mg |
| Carbohydrate compound | 61.0g |
| Sodium salt | 264mg |
In this example, fasting blood glucose levels of cynomolgus monkeys were measured using the hexokinase method. With fasting plasma glucose >7mmol/L as a diagnostic standard, 15 of 31 cynomolgus monkeys developed type 2 diabetes with an incidence of 48.39%.
Comparative example 1
(1) 30 male cynomolgus monkeys of 12 to 21 years old from the same origin as in example 1 were selected.
(2) Feeding the cynomolgus monkey in the step (1) three times per day, 7: 30-8: 00 the first feeding of 120 g of conventional feed (nutrient content shown in table 7), 14: 00-14: 30 green feed with the same ingredients as in example 1 for the second feeding, 17: 00-17: the conventional feed is fed for 30 times and 120 g for the third time, all the feed can be completely fed, and the nutrient components of the conventional feed are shown in Table 7.
(3) Feeding was carried out in the same manner as in step (2) except that the feeding was started and ended at the same time as in example 1.
In this comparative example, the fasting blood glucose level of the cynomolgus monkey was measured in the same manner as in example 1. With fasting blood glucose >7mmol/L as the diagnostic standard, type 2 diabetes did not appear in 30 cynomolgus monkeys, with an incidence of 0%.
TABLE 7
| Item | Each 100g |
| (Energy) | 1539kj |
| Protein | 18.5g |
| Fat | 5.8g |
| Cholesterol | 0mg |
| Carbohydrate compound | 59.4g |
| Sodium salt | 279mg |
Test example 1
The cynomolgus monkey model obtained in example 1 was compared with the finger blood glucose level, peripheral blood glucose level, c-peptide level in blood, insulin level, and glycated hemoglobin level of the cynomolgus monkey after feeding in comparative example 1. As shown in FIG. 1, HCD shows the results of the test on the cynomolgus monkey (model group) in example 1, CON shows the results of the test on the cynomolgus monkey (control group) in control example 1, wherein FIG. 1A shows the results of comparison of finger blood glucose levels, FIG. 1B shows the results of comparison of peripheral blood glucose levels, FIG. 1C shows the results of comparison of C-peptide levels in blood, FIG. 1D shows the results of comparison of insulin levels, and FIG. 1E shows the results of comparison of glycated hemoglobin levels. ns means P > 0.05, P < 0.0001.
The results of the upper graph show that the finger blood glucose level and the peripheral blood glucose level of the cynomolgus monkey in the model of the example 1 are obviously higher than those of the cynomolgus monkey in the control example 1; example 1 the c-peptide level, insulin level, glycated hemoglobin level in the blood of model cynomolgus monkey were not statistically different from those of comparative example 1.
And the data prompt comprises the following steps: the cynomolgus monkey model similar to human type 2 diabetes can be obtained in 1 year by carrying out long-term mild feeding in a mode that the sugar content and the fat content are lower than those of the traditional high-sugar and high-fat feeding. The explanation about the no significant change in the c-peptide level, insulin level, glycated hemoglobin level in blood compared to control 1 is as follows:
1. the C peptide level in blood can be used for typing diabetes, and in type 1 diabetes (T1DM), the B cells of pancreatic islets are largely destroyed, the C peptide level is low, and the stimulation response to blood sugar is poor; whereas type 2 diabetic patients usually have normal or elevated C-peptide water. Peptide C levels in this model are normal and further evidence for type 2 diabetes.
2. Insulin determination is a reliable method for diagnosing diabetes and its typing, and is also an important index reflecting the function of insulin cell storage and secretion. The fasting insulin level of the type 2 diabetes mellitus patient can be normal or slightly lower than normal, and the fasting insulin level of the type 2 diabetes mellitus model obtained by the method is in a normal range.
3. Glycated hemoglobin may indirectly reflect the average blood glucose level of a patient since the last 3 months. The type 2 diabetes model obtained by the method does not have the increase of glycosylated hemoglobin, and is consistent with the phenomenon of the diabetes animal model obtained by other methods reported at present.
Claims (10)
1. A method for establishing a cynomolgus monkey type 2 diabetes model is characterized by comprising the following steps:
(1) selecting male cynomolgus monkeys with age of 12-21 years old;
(2) feeding the chicken with sugar-containing feed for the first time, feeding the chicken with complementary food for the second time, feeding the chicken with green fodder for the third time, and feeding the chicken with sugar-containing feed for the fourth time;
(3) after feeding for one year according to the mode of the step (2), detecting corresponding indexes, and screening out the cynomolgus monkeys with fasting blood sugar level more than 7 mmol/L;
wherein the complementary food is fed by alternately feeding the red sugar blocks and the biscuits every three days;
the sugar-containing feed is obtained by mixing conventional feed and brown sugar.
2. The method for modeling cynomolgus monkey type 2 diabetes according to claim 1, wherein the content of brown sugar in the sugar-containing feed is 10 to 15% by weight.
3. The method for modeling type 2 diabetes mellitus in cynomolgus monkeys according to claim 1 or 2, wherein the ingredients of the conventional feed comprise corn, soybean meal, and fish meal.
4. The method for modeling cynomolgus monkey type 2 diabetes according to claim 1, wherein the ingredients of the red sugar block comprise white granulated sugar, brown granulated sugar and water;
preferably, the ingredients of the biscuit comprise wheat flour, cream, white granulated sugar, shredded coconut, edible salt, glucose, ammonium bicarbonate and flavourings.
5. The method for modeling type 2 diabetes in cynomolgus monkeys according to claim 1, wherein the first feeding of the sugar-containing diet is carried out at a weight of 120 g;
preferably, the first feeding of the sugar-containing feed is carried out for a period of 7: 30-8: 00.
6. the method for establishing a cynomolgus monkey type 2 diabetes mellitus model according to claim 1, wherein in the complementary diet feeding, the feeding weight when the red sugar block is fed is 30 g, and the feeding weight when the biscuit is fed is 25 g;
preferably, the time for feeding the supplementary material for the second time is 12: 00-12: 30.
7. the method for modeling type 2 diabetes in a cynomolgus monkey of claim 1, wherein the weight of the third feeding of blue food is 100 g;
preferably, the time for feeding the green fodder for the third time is 14: 00-14: 30.
8. the method for modeling type 2 diabetes in cynomolgus monkeys according to claim 1, wherein the fourth feeding of the sugar-containing diet is carried out at a weight of 120 g;
preferably, the fourth feeding of the sugar-containing feed is carried out for a time of 17: 00-17: 30.
9. the method of establishing a cynomolgus monkey type 2 diabetes model according to any of claims 1 to 8 for use in the treatment of diabetes.
10. The use according to claim 9, wherein the cynomolgus monkey type 2 diabetes model constructed by the method is used for discovering a therapeutic drug for type 2 diabetes.
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| US20130149733A1 (en) * | 2010-03-26 | 2013-06-13 | West China Hospital, Sichuan University | Establishment of rhesus monkey model of autoimmunity type 1 diabetes |
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