Application of transcription factor KLF16 protein in preparing drugs for preventing and treating diseases related to abnormal lipid and glucose metabolism

A technology of transcription factors and glucose metabolism, which is applied in the field of biomedicine, can solve the problems of the development of cancer with limited neurological function, and achieve the effects of inhibiting lipid synthesis and deposition, inhibiting hepatic gluconeogenesis, and reducing blood sugar and blood lipid levels

Inactive Publication Date: 2020-08-14
GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, research on KLF16 is often limited to neurological function and its impact on cancer development
There is no research in the existing public literature showing that KLF16 is related to abnormal glucose and lipid metabolism, especially related to metabolic diseases with elevated lipids and sugar

Method used

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  • Application of transcription factor KLF16 protein in preparing drugs for preventing and treating diseases related to abnormal lipid and glucose metabolism
  • Application of transcription factor KLF16 protein in preparing drugs for preventing and treating diseases related to abnormal lipid and glucose metabolism
  • Application of transcription factor KLF16 protein in preparing drugs for preventing and treating diseases related to abnormal lipid and glucose metabolism

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0061] Example 1 In the liver of mice with abnormal glucose and lipid metabolism, Klf16 gene expression is dysregulated and sensitive to nutritional status

[0062] In order to identify novel transcription factors of abnormal hepatic glucose metabolism in obesity and diabetes, mRNA microarray analysis was performed on the livers of C57BL / 6J mice, db / db mice, DIO mice and ob / ob mice.

[0063] 1. Experimental method:

[0064] Both db / db mice and ob / ob mice were purchased from the Experimental Animal Center of Nanjing University, and C57BL / 6J mice were purchased from the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine. C57BL / 6J mice were fed a 60% high-fat diet for 12 weeks to establish a DIO mouse model. Normal mice were divided into Ad-shLuci group and Ad-shKlf16 group, with 10 mice in each group. db / db mice, DIO mice and ob / ob mice were divided into Ad-GFP group and Ad-Klf16 group, with 10 mice in each group.

[0065] After fasting for 4 h...

Embodiment 2

[0071] Example 2 In primary liver cells, overexpression of Klf16 inhibits glycogenogenesis by inhibiting PGC-1α

[0072] 1. Experimental method:

[0073] C57BL / 6J mice used to isolate primary liver cells were purchased from the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine.

[0074] Taking C57BL / 6J mice aged 6-8 weeks as the research object, primary liver cells were isolated by portal vein infusion of collagenase, cultured in 1640 medium, stimulated for 24 hours by giving forskolin (forskolin, FSK, 10μM) Methods The model of gluconeogenesis was constructed. Infection with Ad-KLF16 and Ad-PGC-1a for 24 hours to change the expression of KLF16 and PGC-1a, respectively, for specific research.

[0075] 2. Experimental results

[0076] figure 2 Among them, Ad-gfp refers to the adenovirus carrying the green fluorescent protein gene; Ad-Klf16 refers to the adenovirus carrying the Klf16 gene; Ad-Pgc-1α refers to the adenovirus carrying the Pgc-...

Embodiment 4

[0089] Example 4 Overexpression of KLF16 in the liver protects mice from high-fat diet-induced hyperglycemia

[0090] On the basis of the studies in Examples 1-3 above, the effect of KLF16 on abnormal glucose metabolism in DIO mice induced by a high-fat diet was studied.

[0091] 1. Experimental method:

[0092] C57Bl / 6J mice purchased from the Experimental Animal Center of Guangzhou University of Traditional Chinese Medicine were fed a 60% high-fat diet (HFD) for 12 weeks to establish a DIO mouse model. KLF16 was overexpressed by tail vein injection of AAV-egfp virus and AAV-Klf16 virus. After 6 weeks, these DIO mice were divided into 3 groups and subjected to 3 treatments respectively: (1) DIO mice were starved for 16h, and after injecting 2g / kg glucose Detect changes in blood glucose at different time points, and conduct glucose tolerance test (GTT); (2) DIO mice were starved for 6 hours, injected with 0.75U / kg insulin, detect changes in blood glucose at different time poi...

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Abstract

The invention provides an application of a transcription factor KLF16 protein in the preparation of drugs for preventing and treating diseases related to abnormal lipid and glucose metabolism. The transcription factor KLF16 protein provided by the invention significantly reduces the blood sugar and blood lipid level in disease model animals by mediating and regulating the expression of gluconeogenesis-related genes, and has effects of inhibiting gluconeogenesis and inhibiting lipid synthesis and deposition, and thereby inhibits the progress of hyperglycemia and hyperlipidemia. Therefore, the transcription factor KLF16 protein has the potential of preventing and treating diseases caused by hyperglycemia and hyperlipidemia such as diabetes, diabetic complications, obesity, hyperinsulinemia,hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, and arteriosclerosis, and a new target for the prevention and treatment of the above-mentioned diseases, especially type II diabetes and obesity is provided. The KLF16 protein has no toxic side effects, has good safety, can adapt to the industrial application of new drugs, and has good clinical application prospect.

Description

technical field [0001] The invention belongs to the technical field of biomedicine. Specifically, it relates to the application of the transcription factor KLF16 protein in the preparation of drugs for the prevention and treatment of diseases related to abnormal lipid and glucose metabolism. More specifically, it relates to the application of transcription factor KLF16 protein in the preparation and prevention of hyperglycemia, hyperlipidemia, obesity and other diseases caused by abnormal lipid and glucose metabolism. Background technique [0002] Disorders of glucose and lipid metabolism can cause a variety of metabolic diseases, such as central obesity, diabetes or impaired glucose regulation, hypertension, dyslipidemia, etc., and insulin resistance is the common pathological basis of these diseases. Glucolipid metabolism disorder first involves tissues such as liver, pancreas and skeletal muscle, and excessive hepatic glucose output is a significant sign of type II diabe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K38/17A61K48/00A61K45/06A61K47/46A61P3/10A61P3/06A61P3/04A61P9/10A61P5/50A61P9/12A61P9/04A61P7/10A61P19/06
CPCA61K38/1709A61K45/06A61K47/46A61K48/0008A61K48/005A61P3/04A61P3/06A61P3/10A61P5/50A61P7/10A61P9/04A61P9/10A61P9/12A61P19/06A61K2300/00
Inventor 高永
Owner GUANGZHOU UNIVERSITY OF CHINESE MEDICINE
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