Novel target for developing medicaments for treating diabetes, obesity and cardiovascular diseases and biological characteristics thereof

A technology for diabetes, new targets, applied in the field of new targets and their biological properties for the development of drugs for diabetes, obesity and cardiovascular disease, and can solve poorly understood problems

Inactive Publication Date: 2011-01-26
史裕昆
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  • Abstract
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  • Claims
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Problems solved by technology

However, little is known about the molecular mechanisms underlying the diet-induced obesity pathogenesis of biphosphatidylglycerol remodeling and mitochondrial dysfunction with insulin resistance

Method used

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  • Novel target for developing medicaments for treating diabetes, obesity and cardiovascular diseases and biological characteristics thereof
  • Novel target for developing medicaments for treating diabetes, obesity and cardiovascular diseases and biological characteristics thereof
  • Novel target for developing medicaments for treating diabetes, obesity and cardiovascular diseases and biological characteristics thereof

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Embodiment Construction

[0020] 1. Animals and reagents

[0021] Male and female C57BL / 6 mice, 4 to 6 weeks old, were purchased from Jackson Laboratories. All animals were housed in an environment with a diurnal photoperiod, free access to water and standard mouse cages, and a high-fat diet for research. 60% of the calories come from lard or soybean oil. All animals used in this study were approved by the Animal Health Agency, following NIH protocol guidelines. The polyclonal antibodies used in this study include AKT antibody, phosphorylated AKT antibody (Ser473), phosphorylated AKT antibody (Thr308), AMPKα antibody, phosphorylated AMPKα antibody (Thr172), IRS-1 antibody, phosphorylated IRS1 antibody (Ser302) and phosphorylated stress-activated protein kinase / JNK antibody (Thr183 / Tyr185), Cell Signaling Technology. The polyclonal antibody of JNK1 was purchased from Santa Cruz Biotechnology Company, and the donkey anti-rabbit IgG horseradish peroxidase conjugated antibody was purchased from GE Healt...

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Abstract

The invention discloses acyltransferase ALCAT1 serving as a target for developing medicaments for treating diabetes, obesity and cardiovascular diseases. The invention discloses that: ALCAT1 causes pathological reconstruction action of diphosphatidyl glycerol under the oxidative stress condition, and thus leads to mitochondria dysfunction, insulin resistance and other symptoms related to diet-induced obesity, wherein the ALCAT1 can be used as a regulatory gene of oxidative stress and mitochondria dysfunction in metabolic diseases and aging; and increased active oxygen causes the change of diphosphatidyl glycerol conformation to increase the ALCAT1, which leads to mitochondrial proton leakage, oxidative stress and mitochondria dysfunction, and further aggravates the insulin resistance and metabolic defects. Therefore, a chemical reagent inhibiting the ALCAT1 can provide a novel method for treating the obesity and related metabolic complications.

Description

technical field [0001] The present invention relates to the important role played by ALCAT1 (precardiophosphatidyltransferase) in the change of diphosphatidylglycerol chloride conformation in the process of mitochondrial dysfunction and insulin resistance leading to diet-induced obesity. new targets of the disease. Background technique [0002] Mitochondrial dysfunction has recently been identified as a common complication of metabolic obesity. However, these mitochondrial hyperactivity are associated with severe insulin resistance in Asian Indians. Attenuated oxidative phosphorylation activity in mice deficient in AIF (mitochondrial flavin protein apoptosis-inducing factor) protects against diet-induced obesity and insulin resistance. In addition, all insulin sensitizers, including the most popular antidiabetic drugs thiazoles and metformin, inhibit mitochondrial complex I activity. Therefore, the molecular mechanism of the pathogenic role of mitochondrial dysfunction in...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/02A61K49/00A01K67/027
Inventor 史裕光
Owner 史裕昆
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