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Application of FBXW7 or up-regulator thereof in preparing medicament for treating diabetes and preventing and treating tumorigenesis of diabetic individuals

A technology of diabetes and diabetic blood vessels, applied in the field of biomedicine, can solve the problem of not equal to diabetes and obesity mouse models.

Active Publication Date: 2020-03-10
SHANGHAI FIRST PEOPLES HOSPITAL
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although the study showed that the overexpression of FBXW7 in the liver of obese mouse models prevents insulin resistance, lowers blood sugar, and prevents obesity from developing into diabetes, the obese mouse model is not equivalent to hyperglycemia or diabetes. So far, no literature has reported the role of FBXW7 in the prevention and treatment of diabetic vascular complications and tumors

Method used

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  • Application of FBXW7 or up-regulator thereof in preparing medicament for treating diabetes and preventing and treating tumorigenesis of diabetic individuals
  • Application of FBXW7 or up-regulator thereof in preparing medicament for treating diabetes and preventing and treating tumorigenesis of diabetic individuals
  • Application of FBXW7 or up-regulator thereof in preparing medicament for treating diabetes and preventing and treating tumorigenesis of diabetic individuals

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Experimental program
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Embodiment 1

[0081] 1. Method

[0082] 1. Construction of viral vector overexpressing EWS (name: E-OE) or Fbxw7 (name: F-OE) protein

[0083] (1) Amplify the nucleotide sequences of EWS and Fbxw7 by PCR reaction (the EWS sequence is shown in SEQ ID NO: 1, and the Fbxw7 sequence is shown in SEQ ID NO: 2), and the two ends are connected to EcoRI and BamHI restriction sites point;

[0084] (2) Double-enzyme digestion PCR product and purification;

[0085] (3) H201pAdeno-MCMV-EGFP-3FLAG vector plasmid (Shanghai Heyuan Biotechnology Co., Ltd.) was also double-enzyme digested, the large fragment was recovered and purified, and the EWS or Fbxw7 gene fragment in step (2) was inserted by molecular cloning technology instead of EGFP to the EcoRI and BamHI restriction sites of the shuttle plasmid;

[0086] (4) Screening transformants by colony PCR, and the screened positive clones are verified by sequencing;

[0087] (5) Sequencing to verify the correct clone, and perform high-purity plasmid extr...

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Abstract

The invention relates to an application of F-box / WD40domain protein 7 (FBXW7) or an up-regulator thereof in preparing a medicament for treating diabetes and preventing and treating tumorigenesis of diabetic individuals. The invention finds that the FBXW7 obviously reduces the high ROS level and excessive activation of poly-(ADP-ribose)polymerase (PARP) in diabetic macrovascular and microvascular endothelia and retinal tissues; the FBXW7 protein repairs damaged DNA by activating a homologous recombination repair (HR) pathway and a non-homology end joining (NHEJ) pathway, so that high-sugar toxicity of the vascular endothelia is relieved, and a retinal protection effect is shown; and the FBXW7 can obviously enhance catabolism and AMPK activity of macrovascular endothelial cells and reduce JNK activity. It suggests that FBXW7 or the up-regulator thereof can be used for preparing medicines for relieving dysfunction of diabetic vascular endothelia, or strengthening repair of DNA damage, ortreating diabetes, or preventing and treating diabetic complications, or for preventing and treating tumorigenesis of diabetic individuals.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to the application of FBXW7 or its up-regulator in preparing medicines for treating diabetes and preventing and treating the occurrence of tumors in individuals with diabetes. Background technique [0002] Diabetes mellitus (DM) is a lifelong metabolic disease characterized by chronic hyperglycemia. Diabetic vascular disease is a characteristic pathological change of diabetes, and it is the main cause of disease and disability in patients. Long-term high blood sugar will damage the large blood vessels and micro blood vessels, which will seriously endanger the heart, brain, kidney, peripheral nerves, eyes, feet, etc. [1]. According to the statistics of the American Diabetes Association (ADA), the risk of complications in patients with diabetes for more than 3 years is more than 46%; the probability of complications in patients with diabetes for more than 5 years is more than 61%...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K45/00A61P3/10A61P9/10A61P13/12A61P35/00
CPCA61K45/00A61P3/10A61P9/10A61P13/12A61P35/00
Inventor 韦芳许迅邓骏杰姚谢怡顾青
Owner SHANGHAI FIRST PEOPLES HOSPITAL
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