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CN-121971588-A - Application of TAS2R14 to regulation of ADAMTS1 in treatment of insulin resistance

CN121971588ACN 121971588 ACN121971588 ACN 121971588ACN-121971588-A

Abstract

The invention discloses application of TAS2R14 to regulation of ADAMTS1 in treating insulin resistance. In particular, the invention provides the use of a TAS2R14 protein, mRNA, or expression vector thereof, for the preparation of a formulation or composition for (a) reducing oxidative stress and (b) reducing Insulin Resistance (IR). The formulations or compositions of the present invention are effective in reducing insulin resistance and oxidative stress.

Inventors

  • LI XIANGQI
  • LIU LIANYONG
  • MA JUNHUA
  • PENG LI
  • LI CHENXI
  • DI XIN
  • NI MINJIE
  • CHEN JIAJUN
  • ZHU QINGYUN
  • ZHU HONGLING

Assignees

  • 上海市浦东新区公利医院(第二军医大学附属公利医院)

Dates

Publication Date
20260505
Application Date
20250711

Claims (10)

  1. 1. Use of a TAS2R14 protein, mRNA, or expression vector thereof, for the preparation of a formulation or composition for: (a) Reducing oxidative stress; (b) Decreasing Insulin Resistance (IR).
  2. 2. The use according to claim 1, wherein the composition is a pharmaceutical composition.
  3. 3. A pharmaceutical composition, characterized in that, the pharmaceutical composition comprises: (a1) TAS2R14 protein, mRNA, or expression vector thereof; (a2) ADAMTS1 protein, mRNA, or expression vector thereof, and (B) A pharmaceutically acceptable carrier.
  4. 4. A combination of formulations, comprising: (a) A therapeutic agent comprising a TAS2R14 protein, mRNA, or expression vector thereof, and (B) Detection reagent the detection reagent is a detection reagent for detecting the quantity of ADAMTS 1.
  5. 5. Use of a pharmaceutical composition according to claim 3 or a combination of formulations according to claim 4 for the preparation of a medicament for reducing insulin resistance.
  6. 6. A medicine box is characterized in that, the kit comprises: (1) The formulation combination of claim 4, and (2) Instructions that use a detection reagent to detect the amount (or level) C1 of ADAMTS1 in a biological sample to be tested of a test subject, and if C1 is less than a control reference value C0, then use a therapeutic agent to treat the test subject.
  7. 7. The kit of claim 6, wherein the biological sample to be tested is hepatic vascular endothelial cells.
  8. 8. A method of reducing insulin resistance in hepatic vascular endothelial cells in vitro under high sugar (HG) induction conditions comprising the step of transfecting said hepatic vascular endothelial cells with OE-TAS2R 14.
  9. 9. The method of claim 8, wherein the OE-TAS2R14 is a TAS2R14 overexpression vector.
  10. 10. The method of claim 8, wherein the method is non-diagnostic and non-therapeutic.

Description

Application of TAS2R14 to regulation of ADAMTS1 in treatment of insulin resistance Technical Field The invention belongs to the field of biomedicine, and particularly relates to application of TAS2R14 to regulation of ADAMTS1 in treating insulin resistance. Background The reduced long-term responsiveness of Insulin Resistance (IR) target organs or tissues to insulin is the central pathophysiological mechanism of progression of type 2 diabetes (T2 DM). Hyperglycemia, a major cause of diabetes and its complications, has been recognized as one of the important factors responsible for IR as a prominent metabolic disorder. The action of insulin is not limited to metabolic cells but also to blood vessels, in particular vascular endothelial cells. Thus, attention to endothelial IR may be an alternative approach to find new therapeutic strategies for alleviating IR-related metabolic diseases. Therefore, it is of great importance in the art to develop a drug that effectively reduces insulin resistance and thus effectively treats IR-related metabolic diseases. Disclosure of Invention The invention provides a medicament for effectively reducing insulin resistance and thus effectively treating IR related metabolic diseases. In a first aspect of the invention there is provided the use of a TAS2R14 protein, mRNA, or expression vector thereof (in particular stability modification or chiral molecules and structures) for the preparation of a formulation or composition for: (a) Reducing oxidative stress; (b) Decreasing Insulin Resistance (IR). In another preferred embodiment, the TAS2R14 protein, mRNA, or expression vector thereof is a stability modified TAS2R14 protein, mRNA, or expression vector thereof. In another preferred embodiment, the formulation is a laboratory formulation. In another preferred embodiment, the composition is a pharmaceutical composition. In another preferred embodiment, the insulin resistance is insulin of endothelial cells. In another preferred embodiment, the formulation or composition is also used for treating type 2 diabetes (T2 DM). In another preferred embodiment, the drug is in the form of a Lipid Nanoparticle (LNP) having encapsulated therein a stability modifying mRNA (partial base methylation or other modification or LNA) of TAS2R 14. In another preferred embodiment, the lipid nanoparticle further encapsulates an mRNA of ADAMTS 1. In another preferred embodiment, the insulin resistance is insulin resistance with low expression of TAS2R 14. In another preferred embodiment, the insulin resistance is insulin resistance with low expression of ADAMTS 1. In a second aspect of the present invention, there is provided a pharmaceutical composition comprising: (a1) TAS2R14 protein, mRNA, or expression vector thereof; (a2) ADAMTS1 protein, mRNA, or expression vector thereof, and (B) A pharmaceutically acceptable carrier. In another preferred embodiment, the pharmaceutical composition further comprises an additional agent for reducing oxidative stress and/or reducing insulin resistance. In another preferred embodiment, the pharmaceutically acceptable carrier is a Lipid Nanoparticle (LNP). In another preferred embodiment, the pharmaceutical composition is a lipid nanoparticle pharmaceutical formulation and the lipid nanoparticle is encapsulated with (a 1) a TAS2R14 protein, mRNA, or expression vector thereof, and (a 2) an ADAMTS1 protein, mRNA, or expression vector thereof. In a preferred aspect of the present invention, there is provided a lipid nanoparticle pharmaceutical formulation comprising: (1) A therapeutic agent selected from the group consisting of (a 1) a TAS2R14 protein, mRNA, or expression vector thereof, (a 2) an ADAMTS1 protein, mRNA, or expression vector thereof, or a combination thereof; (2) Lipid nanoparticles encapsulating the therapeutic agent, and (3) A pharmaceutically acceptable carrier. In another preferred embodiment, the lipid nanoparticle further comprises a targeting element, the targeting element targeting vascular endothelial cells. In another preferred embodiment, the vascular endothelial cells are hepatic vascular endothelial cells. In another preferred embodiment, the pharmaceutical formulation is in the form of an injectable formulation. In another preferred embodiment, the lipid nanoparticle comprises an ionizable lipid, lecithin, phospholipid, and PEG lipid. In another preferred embodiment, the lipid nanoparticle is an ionizable lipid. In another preferred example, the encapsulation efficiency of the encapsulation is more than or equal to 80%, and the average particle size of the encapsulated stock solution after encapsulation is 50-150nm. In another preferred embodiment, the pharmaceutical composition further comprises a pharmaceutically acceptable adjuvant. In another preferred embodiment, the pharmaceutically acceptable excipients are selected from the group consisting of diluents, excipients, surfactants, lubricants, disintegrants, or combinations thereof. In ano