Function and application of G-protein signaling regulator 6 and its inhibitors in the treatment of fatty liver and type Ⅱ diabetes

Abstract

The invention discloses a function and an application of an RGS6 (regulator of G protein signaling 6) gen in treatment of fatty liver and diabetes mellitus diseases. An RGS6 gene knockout mouse and a wild type C57 mouse are taken as experimental subjects, by means of a high-fat DIO (diet induced obesity) mouse model, a result shows that compared with the wild type C57 mouse, the weight of the RGS6 gene knockout mouse is reduced, the fasting blood-glucose level is lower than that of the WT mouse in a control group, and the liver function is obviously better than that of the WT mouse. An IPGTT (intraperitoneal glucose tolerance test) shows that the glucose tolerance ability of the RGS6 gene knockout mouse is improved obviously. Results of determination in general appearance of the mouse liver, the liver weight, the liver / weight ratio and activity of a liver function related enzyme prove that fatty liver lesions of the RGS6-KO (knockout) mouse in a high fat diet group are relieved obviously, and the lipid accumulation is reduced remarkably. Therefore, the RGS6 can be taken as a target for screening drugs for treating fatty liver and / or T2DM, and an RGS6 inhibitor can be used for preparing the drugs for treating fatty liver and / or T2DM.

Description

technical field

[0001] The present invention belongs to the field of gene function and application, in particular to a G protein signaling regulator 6 (Regulator of G protein signaling 6, RGS6) used as a drug target in screening for the prevention, alleviation and / or treatment of fatty liver and / or type II diabetes application in medicines. Background technique

[0002] With the increase of aging population, urbanized life and changes in lifestyle, obesity, non-alcoholic fatty liver disease, metabolic syndrome and diabetes and other metabolic abnormalities have increased sharply, and have now become an important hazard to global public health.

[0003] Diabetes is caused by various factors such as genetic factors, immune dysfunction, microbial infection, and mental factors. The body's islet function is reduced, insulin resistance, and finally leads to a series of metabolic disorder syndromes such as sugar, protein, fat, water, and electrolytes. According to statistics, ther...

Examples

Embodiment 1

[0058] [Example 1] Fatty liver in mice and type Ⅱ diabetes model (diet induced obesity, DIO) were obtained

[0059] (1) Grouping of experimental animals: 8-week-old, male, WT mice and RGS6-KO mice were selected and given two special diets, D12942 high-fat diet (High fat diet, HFD) and D12450B low-fat diet (Normal chow , NC) feeding, that is WTNC group, KO NC group, WT HFD group, KO HFD group a total of 4 groups.

[0060] (2) The model induces the operation process through high-fat feed:

[0061] WT and KO mice were used to establish DIO models, and phenotype correlation analysis was performed to clarify the role of RGS6 gene on fatty liver and type Ⅱ diabetes. 8-week-old, male, WT mice and RGS6-KO mice were selected and fed with two special diets, D12942 high-fat diet (Highfat diet, HFD) and D12450B low-fat diet (Normal chow, NC), respectively, that is, WT NC group, KO NC group, WT HFD group, KO HFD group, a total of 4 groups. The food intake of the mice was recorded in det...

Embodiment 2

[0062] [Example 2] Determination of mouse body weight and blood sugar level

[0063] (1) Fasting body weight and food intake detection of mice

[0064] 1) Weight detection.

[0065] ①Fasting: fast the mice to be tested at 8:00 am (without water), and start the experimental operation at 2:00 pm.

[0066]② Weighing: Weigh at the 0th week, 4th week, 8th week, and 12th week respectively, put a small plastic bucket on the dynamic electronic balance, grab the mouse, put it into the weighing bucket, measure the body weight and record the data . Feed amount detection: After the weighing operation is completed, add feed to the mice, and record the amount of feed for the mice on the dynamic electronic balance.

[0067] (2) Fasting blood glucose level detection experiment

[0068] All the mice to be tested were fasted from 8:00 am to 2:00 pm (without water), that is, the experimental operation was started after 6 hours of fasting.

[0069] ① Blood glucose meter preparation: Check th...

Embodiment 3

[0074] [Example 3] Glucose tolerance test (intraperitoneal glucose tolerance test, IPGTT)

[0075] In the 12th week of the experiment, the intraperitoneal glucose injection test (IPGTT) was performed to evaluate the glucose tolerance of the mice.

[0076] (1) Before measuring blood glucose, measure the fasting body weight of the mice, and calculate the injection volume of glucose based on 10 μL / g.

[0077] (2) First detect the fasting blood glucose at 0 minutes before the glucose injection, and inject the glucose solution intraperitoneally quickly after the detection is completed.

[0078] (3) Operation method of intraperitoneal injection: ①Fix the mouse; grab the mouse, grab the tail of the mouse with the little finger and ring finger of the left hand, and grab the neck of the mouse with the other three fingers, so that the head of the mouse is downward, and the The abdomen of the mouse is fully exposed. ②Needle positioning and injection: insert the needle from the side of ...

technical field

[0001] The present invention belongs to the field of gene function and application, in particular to a G protein signaling regulator 6 (Regulator of G protein signaling 6, RGS6) used as a drug target in screening for the prevention, alleviation and / or treatment of fatty liver and / or type II diabetes application in medicines. Background technique

[0002] With the increase of aging population, urbanized life and changes in lifestyle, obesity, non-alcoholic fatty liver disease, metabolic syndrome and diabetes and other metabolic abnormalities have increased sharply, and have now become an important hazard to global public health.

[0003] Diabetes is caused by various factors such as genetic factors, immune dysfunction, microbial infection, and mental factors. The body's islet function is reduced, insulin resistance, and finally leads to a series of metabolic disorder syndromes such as sugar, protein, fat, water, and electrolytes. According to statistics, ther...

Examples

Embodiment 1

[0058] [Example 1] Fatty liver in mice and type Ⅱ diabetes model (diet induced obesity, DIO) were obtained

[0059] (1) Grouping of experimental animals: 8-week-old, male, WT mice and RGS6-KO mice were selected and given two special diets, D12942 high-fat diet (High fat diet, HFD) and D12450B low-fat diet (Normal chow , NC) feeding, that is WTNC group, KO NC group, WT HFD group, KO HFD group a total of 4 groups.

[0060] (2) The model induces the operation process through high-fat feed:

[0061] WT and KO mice were used to establish DIO models, and phenotype correlation analysis was performed to clarify the role of RGS6 gene on fatty liver and type Ⅱ diabetes. 8-week-old, male, WT mice and RGS6-KO mice were selected and fed with two special diets, D12942 high-fat diet (Highfat diet, HFD) and D12450B low-fat diet (Normal chow, NC), respectively, that is, WT NC group, KO NC group, WT HFD group, KO HFD group, a total of 4 groups. The food intake of the mice was recorded in det...

Embodiment 2

[0062] [Example 2] Determination of mouse body weight and blood sugar level

[0063] (1) Fasting body weight and food intake detection of mice

[0064] 1) Weight detection.

[0065] ①Fasting: fast the mice to be tested at 8:00 am (without water), and start the experimental operation at 2:00 pm.

[0066]② Weighing: Weigh at the 0th week, 4th week, 8th week, and 12th week respectively, put a small plastic bucket on the dynamic electronic balance, grab the mouse, put it into the weighing bucket, measure the body weight and record the data . Feed amount detection: After the weighing operation is completed, add feed to the mice, and record the amount of feed for the mice on the dynamic electronic balance.

[0067] (2) Fasting blood glucose level detection experiment

[0068] All the mice to be tested were fasted from 8:00 am to 2:00 pm (without water), that is, the experimental operation was started after 6 hours of fasting.

[0069] ① Blood glucose meter preparation: Check th...

Embodiment 3

[0074] [Example 3] Glucose tolerance test (intraperitoneal glucose tolerance test, IPGTT)

[0075] In the 12th week of the experiment, the intraperitoneal glucose injection test (IPGTT) was performed to evaluate the glucose tolerance of the mice.

[0076] (1) Before measuring blood glucose, measure the fasting body weight of the mice, and calculate the injection volume of glucose based on 10 μL / g.

[0077] (2) First detect the fasting blood glucose at 0 minutes before the glucose injection, and inject the glucose solution intraperitoneally quickly after the detection is completed.

[0078] (3) Operation method of intraperitoneal injection: ①Fix the mouse; grab the mouse, grab the tail of the mouse with the little finger and ring finger of the left hand, and grab the neck of the mouse with the other three fingers, so that the head of the mouse is downward, and the The abdomen of the mouse is fully exposed. ②Needle positioning and injection: insert the needle from the side of ...

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