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Application of Galectin-3 as target in searching pancreas islet protection function drugs or biological agents

A technology for biological preparations and pancreatic islets, applied in the field of medicine, can solve the problems of inability to protect β-cell type 2 diabetes, and achieve the effects of protecting islet β-cells, increasing insulin secretion, and improving insulin secretion.

Pending Publication Date: 2021-10-22
INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Therefore, using the relationship between Galectin-3 and insulin secretion, how to apply Galectin-3 to anti-diabetes will have important practical significance for solving the problem that existing drugs cannot protect β cells or prevent type 2 diabetes

Method used

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  • Application of Galectin-3 as target in searching pancreas islet protection function drugs or biological agents
  • Application of Galectin-3 as target in searching pancreas islet protection function drugs or biological agents
  • Application of Galectin-3 as target in searching pancreas islet protection function drugs or biological agents

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Effects of Galectin-3 on Glucose-Stimulated Insulin Secretion (GSIS) of Rat or Mouse Pancreatic β-Cells.

[0032] Treatment group cells: first prepare Galectin-3 of corresponding concentration (see figure 1A-C, respectively 250ng / mL, 125ng / mL, 80ng / mL) in normal culture medium (DMEM high glucose medium, 15% serum, 50μM β-mercaptoethanol), control group cells: add Galectin-3 vehicle (containing 0.1% BSA in PBS); after 4 hours of treatment, the medium was discarded, and the KRHB solution containing 2.8mM glucose (NaCl 119mM, KCl 4.8mM, CaCl 2 2.5mM, MgSO 4 ·7H 2 O 1.2mM, KH 2 PO 4 1.2mM, HEPES10mM, BSA 0.1%) and washed twice, and then use the low-sugar solution to prepare the corresponding concentration of solvent or Galectin-3 starved cells for 1h, and then use the KRHB solution containing 2.8mM or 16.8mM glucose to prepare the corresponding concentration of vehicle or Cells were stimulated with Galectin-3 for 1 h, the cell supernatant was collected, and insulin w...

Embodiment 2

[0035] Effect of Galectin-3 on GSIS of primary mouse islets.

[0036] Isolation of primary islets: mice were fasted for 12-16 hours, anesthetized with pentobarbital sodium or chloral hydrate; about 3 mL of pre-cooled collagenase type V (Sigma) was injected into the common bile duct to fill the pancreas; the pancreas was removed and placed in Put in a 15mL centrifuge tube containing 10mL Hank's solution (preheated at 37°C), in a water bath at 37°C for 10min, and vibrate into sand; pass through a 30-mesh cell sieve (pore size 600μm), and connect the filtrate with an ice-bathed watch glass; then, use Pre-cooled 40mL Hank's solution containing 10% bovine serum was sieved to stop the digestion, and the cell suspension was collected in a 50mL centrifuge tube. Centrifuge at 4°C and 1000rpm for 2min, and remove the supernatant; 15mL of Hank's solution, centrifuge at 4°C and 1000rpm for 2min, remove the supernatant, add DMEM low-glucose medium (containing 10% FBS) to the pellet to blow...

Embodiment 3

[0040] Non-glucose-stimulated insulin secretion.

[0041] Insulin secretion is not only stimulated by glucose, amino acids and glucagon-like peptide-1 (GLP-1) can also stimulate insulin secretion, and GLP-1 stimulates insulin secretion is glucose-dependent. To investigate whether Galectin-3 specifically inhibits glucose-stimulated insulin secretion, its effect on arginine (Arg)- and GLP-1-stimulated insulin secretion was examined.

[0042] Specific method: Min6 cells were first treated with vehicle (Veh, negative control group) and 80ng / mL Galectin-3 until starved for 1 hour, which was the same as that in Example 1. When stimulated by high glucose, arginine or GLP-1 stimulation was added to the corresponding groups according to the experimental design.

[0043] The results showed that Galectin-3 did not affect arginine-stimulated insulin secretion (eg Figure 4 As shown in A), but it has a promoting effect on glucose-dependent GLP-1-stimulated insulin secretion (such as Fi...

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Abstract

The invention relates to the technical field of medicines, and particularly discloses application of galactoside agglutinin 3 as a target in searching pancreas islet protection function drugs or biological agents. Galectin-3 is taken as a target, insulin secretion of beta cells of diabetic animals is improved by inhibiting expression of Galectin-3, pancreas islet beta cells are protected, the purpose of preventing or treating diabetes is further achieved, and the Galectin-3 has important practical significance for overcoming the defect that existing drugs cannot protect beta cells and prevent diabetes.

Description

technical field [0001] The invention belongs to the technical field of medicine, and specifically relates to the application of Galectin-3 as a target in searching for drugs or biological preparations for protecting islet function. Background technique [0002] Obesity and the resulting diabetes are on the rise worldwide. Diabetes is divided into type 1, type 2 and gestational diabetes, and type 2 diabetes accounts for more than 90% of all diabetic patients. Obesity, and consequently type 2 diabetes, is steadily increasing and has become a global health problem. The occurrence of type 2 diabetes is mainly secondary to obesity. When obese, immune cells such as macrophages are produced in large quantities, leading to local or systemic chronic inflammation. Inflammation can promote the occurrence of insulin resistance, which will lead to a compensatory increase in insulin secretion by pancreatic β cells, and eventually damage the function of pancreatic β cells. Insufficient ...

Claims

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Application Information

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IPC IPC(8): A61K45/00A61P3/10A61P5/50
CPCA61K45/00A61P3/10A61P5/50
Inventor 李平平姜茜崔冰赵其锦柳星峰马春晓王树森孔丽娟侯少聪
Owner INST OF MATERIA MEDICA AN INST OF THE CHINESE ACAD OF MEDICAL SCI
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