Use of psat1 and its products in the preparation of drugs for regulating insulin sensitivity
A technology for insulin sensitivity and insulin resistance, which can be used in the field of biomedicine to solve problems such as unclear insulin sensitivity
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Embodiment 1
[0216] Example 1. PAST1 regulates insulin sensitivity in vitro
[0217] In order to study whether PAST1 is involved in the regulation of insulin sensitivity, the inventors infected human liver tumor cell HepG2 and mouse liver primary cells with PAST1 adenovirus (Ad-PSAT1) and control virus green fluorescent protein (Ad-GFP), and detected this Changes in the insulin pathway in both types of cells. The inventors found that in both cells, overexpression of PSAT1 increased insulin-stimulated phosphorylation of protein kinase B (AKT) at serine 473, glycogen synthesis kinase 3β (GSK-3β) 9 Phosphorylation of serine ( figure 1 A).
[0218] The present inventors infected human liver tumor cell HepG2 and mouse liver primary cells with adenovirus (Ad-shPSAT1) targeting small hairpin RNA in the coding region of PSAT1 (Ad-shPSAT1) and control virus scrambled, and found that compared with the control group, Ad-shPSAT1 decreased Increased endogenous PSAT1 protein levels, decreased insulin...
Embodiment 2
[0219] Example 2. In vivo overexpression of PSAT1 improves insulin sensitivity
[0220] In order to explore the effect of PSAT1 on insulin sensitivity in vivo, the inventors injected Ad-PSAT1 or Ad-GFP through the tail vein in male C57BL / 6J wild-type (WT) mice, and found that compared with the control group, Ad-PSAT1 PSAT1 gene and protein levels in the liver of mice in the group were significantly increased ( figure 2 A). Although the body weight and food intake of the mice in the Ad-PSAT1 group did not change, the blood glucose was significantly reduced in the fed and starved state ( figure 2 B). Insulin levels in starved serum did not change, and insulin levels in fed serum decreased significantly ( figure 2 C). Moreover, the HOMA-IR index decreased significantly ( figure 2 D).
[0221] After tail vein injection of mice with Ad-PSAT1 or Ad-shPSAT1, there was no significant change in food intake and body weight ( Figure 11 A-D).
[0222] The inventors tested glu...
Embodiment 3
[0223] Example 3. Knockdown of PAST1 in vivo impairs insulin sensitivity
[0224] The results of Example 2 suggest that knocking down PSAT1 may reduce insulin sensitivity. To test this hypothesis, the inventors injected Ad-shPSAT1 or Ad-scrambled in male C57BL / 6J wild-type (WT) mice. The levels of PSAT1 gene and protein in liver of mice in Ad-shPSAT1 group were significantly decreased ( image 3 A). Although the body weight and food intake of the mice in the Ad-shPSAT1 group did not change, the blood glucose significantly increased in the fed and starved state ( image 3 B). Therefore, although there was no change in serum insulin levels during feeding and starvation, the HOMA-IR index of mice in the Ad-shPSAT1 group was significantly increased ( image 3 C and 3D). Consistent with these results, the inventors found that the mice in the Ad-shPSAT1 group had decreased glucose tolerance and clearance efficiency by GTTs and ITTs, respectively ( image 3 E). Insulin-stimula...
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