Use of mir-451 as a target for regulating blood sugar
A technology of mir-451 and 1.mir-451, which is used in medical preparations containing active ingredients, determination/inspection of microorganisms, metabolic diseases, etc.
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Embodiment 1
[0123] Example 1. Liver miR-451 negatively regulates blood sugar by regulating gluconeogenesis
[0124] Type 2 diabetes was induced by feeding C57BL / 6 mice a high-fat diet, such as figure 1 Shown, the body weight of mice after 12 weeks of high fat diet (HFD) ( figure 1 A), blood sugar ( figure 1 B) are significantly higher than conventional feed fed mice.
[0125] Real-time quantitative PCR detection found that high-fat diet-induced diabetic mice liver miR-451 significantly increased ( figure 1 C). Similarly, miR-451 in the liver of db / db diabetic mice was also significantly increased ( figure 1 D).
[0126] In order to study the role of liver miR-451 in metabolism, the inventors used an adenovirus expression system to observe the effect of overexpressing miR-451 in mouse liver on blood sugar.
[0127] The study found that miR-451 in the liver was significantly increased ( figure 2 A). Compared with the control group, the overexpression of miR-451 could significantly ...
Embodiment 2
[0131] Example 2. Glycerol kinase is the target of miR-451 in the liver
[0132] In order to find the target of miR-451 regulating liver gluconeogenesis, the inventors used targetscan, miRanda and DIANA-microT-CDS three miRNA target prediction software to analyze the possible target of miR-451 in the liver, from Among the predicted targets, molecules that are conserved among species and functionally related to glucose metabolism were selected, and three candidate target molecules, Cab39, Ywhaz and Glycerol kinase (GyK), were obtained.
[0133] The inventors detected the protein expression levels of Cab39 and Ywhaz in the liver of mice overexpressing miR-451, and found that overexpressing miR-451 had no significant effect on the protein levels of Cab39 and Ywhaz, indicating that the function of miR-451 in regulating gluconeogenesis is not It is achieved by regulating the expression of these two proteins.
[0134] The inventors found that there is a miRNA response element (miRN...
Embodiment 3
[0137] Example 3, miR-451 regulates liver gluconeogenesis and blood glucose levels through GyK
[0138]After confirming that liver GyK is the target of miR-451, the function and mechanism of GyK in liver gluconeogenesis were further explored functionally. GyK is the rate-limiting enzyme that catalyzes the conversion of glycerol to glycerol-3-phosphate when glycerol is used as a substrate to participate in gluconeogenesis. After overexpressing GyK in mouse liver ( Figure 4 A), the blood glucose level of mice under free feeding ( Figure 4 B). Overexpression of GyK in mouse liver significantly decreased blood glycerol concentration ( Figure 4 C), and obviously promote gluconeogenesis using glycerol as raw material ( Figure 4 D). These results indicate that GyK regulates gluconeogenesis by regulating glycerol metabolism at the overall level, and GyK plays a role in regulating gluconeogenesis with glycerol as raw material. The pyruvate tolerance experiment showed that the...
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