Compositions for use in the treatment of diabetes

Inactive Publication Date: 2018-08-16
UNIVERSITY OF ULSTER
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a composition for the treatment of diabetes that includes at least one of diindolylmethane, indole-3-carbinol, embelin, [6]-gingerol, and [6]-shogaol, or combinations each other. The composition can be used as a medicament or in the manufacture of a medicament for the treatment of diabetes. The technical effect of the invention is to provide an effective treatment for diabetes that targets the insulin release and utilization pathways in the body. The composition can be administered to patients with diabetes to improve insulin release and lower blood glucose levels. The composition can also be used to alter the expression of genes involved in insulin release, such as GLUT2, GLUT4, and KCNJ11, which are important for insulin secretion. The invention also provides a method for using the composition for the treatment of diabetes.

Problems solved by technology

Diabetes is a major public health challenge with: at least 180 million reported cases of diabetes worldwide—a figure set to more than double by 2030 according to the World Health Organisation (WHO), consumption of 10% of Western healthcare budgets, and around 3.2 million deaths per year resulting from related complications.

Method used

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  • Compositions for use in the treatment of diabetes
  • Compositions for use in the treatment of diabetes
  • Compositions for use in the treatment of diabetes

Examples

Experimental program
Comparison scheme
Effect test

example 1

Expression of GPR84 in BRIN-BD11 Cells and Mouse Islets

[0105]Distribution of insulin and GPR84 were investigated in BRIN-BD11 cells. DAPI (blue) stained nuclei (FIG. 1A), and insulin (green) were distributed across the BRIN-BD11 cells (FIG. 1B) with a similar staining pattern to GPR84 (red) (FIG. 1C). Double immunofluorescence combination of insulin with GPR84 indicated areas of co-localisation (yellow) (FIG. 1D), demonstrating the presence of GPR-a1 in pancreatic beta cells. The distribution of DAPI, insulin, glucagon and GPR84 in mouse pancreatic islets are shown in FIG. 2. DAPI (blue) displayed the nuclei in pancreatic islets (FIGS. 2A, B), GPR84 (green) was expressed throughout the islet with a similar staining pattern to insulin (red) (FIGS. 2C, D). Merge of insulin and GPR84 indicated that insulin secreting beta cells express GPR84 (FIG. 2G) while there was no evidence of the GPR84 receptor in glucagon secreting alpha cells (FIG. 2H). While no co-localisation was displayed on ...

example 2

Effects of Compositions of the Present Invention on Insulin Secretion from BRIN-BD11 Cells

[0106]Insulin releasing properties of compositions of the present invention at 10−12-10−4 mol / L were assessed in clonal BRIN-BD11 cells at 5.6 mM and 16.7 mM glucose. Diindolylmethane at 10−8-10−4 mol / L enhanced insulin release (EC50 1.3×10−7 mol / L) (p−9-10−4 mol / L (EC50 1.0×10−6 mol / L) (p<0.05-p<0.001) (FIG. 4A). No cytotoxicity was found with Diindolylmethane at 5.6 mM glucose (FIG. 3B) and 16.7 mM glucose (FIG. 4B).

[0107]Embelin at 10−9-10−4 mol / L enhanced insulin release (p−7 mol / L) (FIG. 5A) at 5.6 mM basal glucose concentrations. At stimulatory glucose concentrations (16.7 mM glucose), Embelin enhanced insulin release at 10−10-10−4 mol / L (p−7 mol / L) (FIG. 6A). No cytotoxicity was found with Embelin at 5.6 mM glucose (FIG. 5B) and 16.7 mM glucose (FIG. 6B).

[0108]Indole-3-carbinol at 10−7-10−4 mol / L enhanced insulin release (p−6 mol / L) at 5.6 mM basal glucose concentrations. At stimulatory ...

example 3

Effect of Compositions of the Present Invention on Intracellular Ca2+ and cAMP in BRIN-BD11 Cells

[0112]For confirmation of the stimulatory ability of compositions of the present invention on insulin secretion in pancreatic islets and to examine the mechanism of action, beta stimulus coupling pathways and changes in intracellular calcium concentrations and cAMP production in pancreatic BRIN-BD11 cells were examined.

[0113]At both basal and stimulatory glucose concentrations, compositions of the present invention (10−4 mol / L) augmented intracellular Ca2+ concentrations at 5.6 mM glucose (p<0.05-p<0.001) (FIGS. 7-10) with the exception of Indole-3-carbinol and [6]-gingerol. At 16.7 mM glucose, Diindolylmethane, Embelin and [6]-shogaol increased intracellular Ca2+ concentrations (p<0.001) (FIG. 10).

[0114]As shown in FIG. 11, the stimulatory action of Diindolylmethane and Embelin on the insulin secretory pathway involves the cAMP-dependent pathway in pancreatic islets. [6]-shogaol and med...

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Abstract

This invention relates to compositions for use in the treatment of diabetes, for example type-2 diabetes; obesity; and / or metabolic syndrome. Specifically, the invention relates to a composition for use in the treatment of diabetes, the composition comprising at least one of diindolylmethane; indole-3-carbinol; embelin; [6]-gingerol; and [6]-shogaol, or combinations each thereof. Also disclosed is use in the treatment of obesity and use in the treatment of metabolic syndrome.

Description

FIELD OF THE INVENTION[0001]This invention relates to compositions for use in the treatment of diabetes, for example type-2 diabetes; obesity; and / or metabolic syndrome.BACKGROUND TO THE INVENTION[0002]Diabetes is a major public health challenge with: at least 180 million reported cases of diabetes worldwide—a figure set to more than double by 2030 according to the World Health Organisation (WHO), consumption of 10% of Western healthcare budgets, and around 3.2 million deaths per year resulting from related complications. This alarming increase in incidence, coupled with the failure of established anti-diabetic drugs to tightly manage or control diabetes, demonstrates the market need for new innovation.[0003]The worldwide increase in the incidence of obesity, metabolic syndrome, and type-2 diabetes demands the development of new drugs for safe and effective treatment, limiting the progression to long-term diabetic complications.[0004]G-protein coupled receptor 84, also known as GPR8...

Claims

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Application Information

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IPC IPC(8): A61K31/122A61P3/04A61P3/10
CPCA61K31/122A61P3/04A61P3/10A61K2300/00A61K31/7004A61K31/405
Inventor MCKILLOP, AINE MAIREFLATT, PETER RAYMOND
Owner UNIVERSITY OF ULSTER
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