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Application of MS-275 in preparation of drug for promoting insulin secretion

A technology of MS-275, insulin secretion, applied in the field of gene function and application

Inactive Publication Date: 2018-12-14
RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, as a new type of anticancer drug, MS-275 has little research in the field of diabetes, and its effect on the function of islets in vivo and the specific molecular mechanism need to be further explored

Method used

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  • Application of MS-275 in preparation of drug for promoting insulin secretion
  • Application of MS-275 in preparation of drug for promoting insulin secretion
  • Application of MS-275 in preparation of drug for promoting insulin secretion

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] Example 1, Verification of the Effect of MS-275 on Insulin Secretion

[0031] 1.1 Isolation of rat islet cells:

[0032] 1) Configuration of gradient separation solution:

[0033] Solution A: 40ml stock solution + 2ml Hank’s solution without BSA

[0034] Solution B: 6.4ml A solution + 1.1ml BSA-free Hank’s solution

[0035] Solution C: 2.4ml B solution + 2.6ml BSA-free Hank’s solution

[0036] Enzyme for perfusion: 23ml BSA-free Hank’s solution + 1ml XI collagenase stock solution + 1ml 25% BSA (Note: B and C solutions are the doses for 1 rat; each rat is perfused with about 10ml collagenase);

[0037] 2) After preparing the above reagents, add 2ml of 25% BSA to every 500ml of Hank’s, mix well by inverting up and down, and put it on ice for later use;

[0038] 3) Carry out intraperitoneal injection with 10% chloral hydrate at a dose of 1ml / 20g to rats (common male SD rats 6 to 8 weeks old, 200-300g) to anesthetize the rats; to separate the pancreas from the anesthe...

Embodiment 2

[0050] Example 2. Verification of the specific mechanism of MS-275 regulating islet function

[0051] 2.1 Rat islet RNA sequencing experiment

[0052] 1) Isolate rat islets using the method described above, incubate with 3.3mmol / L glucose and 3μmol / L MS-275 for 24h, add 1ml Trizol to each islet to extract sample RNA (Qiagen kit);

[0053] 2) Use Nanodrop to measure the sample RNA concentration, and use a spectrophotometer to measure its purity at 230nm, 260nm and 280nm; the ratio of A260 / A280 of the RNA samples used in this experiment is greater than 1.8, close to 2.0, and the ratio of A260 / A230 is greater than 1.8 , which proves that the RNA samples used in this experiment are of reliable quality, less polluted by proteins and organic matter, and can be used for further experiments.

[0054] 3) Use denatured agarose gel electrophoresis to detect the purity and integrity of the RNA, and select high-quality, complete samples without RNase and DNA contamination for detection;...

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Abstract

The invention discloses the application of MS-275 in preparation of a drug for promoting insulin secretion. MS-275 can be used for protecting pancreatic beta cells by inhibiting a reactive oxygen substance generated by oxidation of glucose. Further, MS-275 also serves as a mitochondrion oxidative phosphorylation gene inhibitor; the inhibitor can be used for regulating insulin secretion stimulatedby high glucose. Compared with the prior art, the invention discovers that MS-275 can be used for promoting insulin secretion and inhibiting oxidative phosphorylation related genes, therefore, MS-275has an effect of protecting the pancreatic beta cells by inhibiting substances such as reactive oxygen and the like generated by oxidation of glucose.

Description

technical field [0001] The invention relates to the technical field of gene function and application, in particular to the use of MS-275 in the preparation of drugs for promoting insulin secretion. Background technique [0002] Pancreatic islets are an important organ that regulates the body's blood sugar homeostasis. It is well known that when blood sugar rises, pancreatic beta cells secrete insulin to prompt blood sugar to drop, and this glucose-stimulated insulin secretion exhibits biphasic characteristics in the body, and the first phase quickly reaches a peak. Mitochondria play an important role in this biphasic secretion, which is called the trigger phase of insulin secretion, followed by a slow and continuous second phase, called the expansion phase of insulin secretion. Diabetes occurs when pancreatic beta cells are damaged or apoptotic, resulting in insufficient insulin secretion, or when insulin resistance results in a relatively insufficient insulin content. [0...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/4406A61P5/50
CPCA61K31/4406A61P5/50
Inventor 王晓周丽斌白梦瑶
Owner RUIJIN HOSPITAL AFFILIATED TO SHANGHAI JIAO TONG UNIV SCHOOL OF MEDICINE
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