Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes

A diabetes drug, sodium hydrosulfide technology, applied in the direction of drug combination, urinary system diseases, metabolic diseases, etc., can solve problems such as adverse side effects, inappropriate use, etc., to increase insulin levels, reduce oxidative stress, and prevent diabetic kidney disease Sign effect

A diabetes drug, sodium hydrosulfide technology, applied in the direction of drug combination, urinary system diseases, metabolic diseases, etc., can solve problems such as adverse side effects, inappropriate use, etc., to increase insulin levels, reduce oxidative stress, and prevent diabetic kidney disease Sign effect

CN103622992AActive Publication Date: 2014-03-12FUDAN UNIV

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  • Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes
  • Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes
  • Application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Example 1 Hydrogen sulfide and its donor sodium hydrosulfide as insulin sensitizer test

[0034] After incubation with different concentrations of NaHS (1-200 μmol / L) for 24 hours, it has no effect on the glucose uptake of normal skeletal muscle cells in the basal state. It was tested whether NaHS has an effect on the glucose uptake of skeletal muscle cells in the presence of insulin. Detect the effects of different concentrations of NaHS (0-200μmol / L) on glucose uptake under insulin stimulation after incubating glucose (5.5μmol / L) and insulin (100nmol / L) resistant skeletal muscle cells for 24 hours, the results show (eg figure 1 shown), the concentration of NaHS increased significantly at 25, 50 and 100 μmol / L 3 H-deoxyglucose uptake, the optimal concentration of NaHS to promote glucose uptake is 100 μmol / L, which is more than doubled compared with the control group, 2.06±0.29 (P<0.01), 25 and 50 μmol / L NaHS respectively increase glucose uptake The ratios are 1.54±0.0...

Embodiment 2

[0050] Example 2 Correlation test between skeletal muscle and fat cells and insulin resistance

[0051] In this embodiment, insulin resistance and diabetes cells widely used in the prior art are used: wherein, the skeletal muscle myoblast cell line is isolated from the primary culture of rat thigh muscle by Yaffe, and can be obtained under certain culture conditions. Fusion forms multinucleated myotubes and striated muscle fibers; adipocyte lines are derived from mouse embryonic fibroblasts, which are cloned and expanded into preadipocyte cell lines, and then induced to differentiate into mature adipocytes by specific differentiation agents;

[0052] 1) Evaluation of insulin sensitivity at the cellular level

[0053] Using isotope-labeled glucose uptake experiments by cells to evaluate the ability of cells to uptake and utilize glucose stimulated by insulin, thereby evaluating insulin sensitivity and judging whether insulin resistance exists;

[0054] Glucose consumption test...

Embodiment 3

[0061] Example 3 Hypoglycemic and insulin-sensitizing effects of hydrogen sulfide and its donor sodium hydrosulfide on type Ⅱ diabetes

[0062] Select 2-month-old GK rats as the animal model of diabetic insulin resistance in this embodiment;

[0063] Insulin tolerance test was routinely carried out, and the experimental results showed that 60 minutes after the chronically administered rats were injected with a certain amount of insulin, the ratio of blood glucose drop in the NaHS 30 μmol / kg group of GK rats was significantly greater than that of the control group (such as Figure 9 shown), the ratio of blood glucose drop in the Wistar rat NaHS 60 μmol / kg group was significantly greater than that of the control group (such as Figure 10 shown); Insulin sensitivity test, using low concentration of insulin (0.4U / kg) to starve Wistar rats for 4 hours, the NaHS 60μmol / kg group was significantly lower than the control group (such as Figure 11 shown), the results show that a small ...

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Abstract

The invention belongs to the field of pharmacy, relates to novel medicinal application of hydrogen sulfide and a donor thereof sodium hydrosulfide to pharmacy, and in particular relates to application of hydrogen sulfide and donor thereof sodium hydrosulfide to preparation of medicament for treating diabetes. The invention adopts the exogenous hydrogen sulfide and its donor sodium hydrosulfide (NaHS) for insulin sensibilization and tests for regulating blood sugar level and increasing insulin level for type II diabetes. Through correlation test of skeletal muscle and adipose cells with insulin resistance, insulin tolerance test by using animal model for diabetes insulin resistance, glucose consumption experiment, animal model experiment for diabetes insulin resistance and NaHS intervention animal experiment, the results show that NaHS can promote glucose uptake in the presence of insulin, thus indicating insulin enhancement effect. The invention of hydrogen sulfide and the donor thereof sodium hydrosulfide can be used as insulin sensitizers and medicaments for regulating blood sugar level and increasing insulin level for type II diabetes.

Description

technical field [0001] The invention belongs to the field of medicine and pharmacy, and relates to the new medicinal application of hydrogen sulfide and its donor sodium hydrosulfide in pharmacy, in particular to the application of hydrogen sulfide and its donor sodium hydrosulfide in the preparation of medicines for treating diabetes. The hydrogen sulfide and its donor sodium hydrosulfide can be used as an insulin sensitizer and a drug for lowering blood sugar and increasing insulin level for type II diabetes. Background technique [0002] The prior art discloses hydrogen sulfide (H 2 S) is a metabolite of cysteine ​​in the human body. Its content in the human body is very low, about 20-50 μmol / L, and it is not easy to be controlled artificially. It is also reported in the literature that H 2 S is a new type of endogenous gas molecule involved in the regulation of cardiovascular activity, and has the purpose of promoting angiogenesis in cardiovascular diseases. [0003] A...

Claims

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Application Information

Patent Timeline
12 Mar 2014
Publication
CN103622992A
IPC
A61K33/04; A61P3/10; A61P5/50; A61P13/12
Inventors
朱依纯; 薛蓉