Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Novel Target for Diagnosis and Treatment of Diabetes and Cardiovascular Diseases

a cardiovascular disease and new target technology, applied in the field of diabetes and cardiovascular disease diagnosis and treatment, can solve the problems of chronic hyperglycemic diabetic state, endocrine effects on distant tissues, and significant decrease in beta cell function and mass, and achieve the effects of improving diabetes, diagnosing and prognosing insulin secretion deficiency and/or beta cell dysfunction, and stimulating insulin secretion

Inactive Publication Date: 2014-12-04
RGT UNIV OF CALIFORNIA
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention provides a new way to diagnose and treat diabetes by targeting a protein called CX3CR1. This protein is involved in regulating insulin secretion and pancreatic islet function. The invention suggests using soluble FKN protein or small molecule agonists of CX3CR1 to improve diabetes by stimulating insulin secretion and improving pancreatic islet function. The invention also suggests using CX3CR1 activators to increase insulin expression and secretion in pancreatic beta cells. Additionally, the invention suggests using soluble FKN to blunt plaque formation and inhibit the recruitment and adhesion of monocytes / macrophages. Overall, the invention provides new tools to diagnose, treat, and prevent diabetes and related complications.

Problems solved by technology

However, when type 2 diabetes emerges, beta cell function and mass are significantly decreased, with insufficient insulin secretion to compensate for the insulin resistance, resulting in the chronic hyperglycemic diabetic state.
Furthermore, soluble FKN can exert paracrine effects in the extracellular space and can also enter the circulation to potentially cause endocrine effects on distant tissues (Shah et al., 2011).

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Novel Target for Diagnosis and Treatment of Diabetes and Cardiovascular Diseases
  • Novel Target for Diagnosis and Treatment of Diabetes and Cardiovascular Diseases
  • Novel Target for Diagnosis and Treatment of Diabetes and Cardiovascular Diseases

Examples

Experimental program
Comparison scheme
Effect test

example 1

Experimental Procedures

Animals and Treatments

[0062]7 week old male C57BL / 6N and CX3CR1 knockout mice were purchased from Taconic (USA). GTT and ITT results from the CX3CR1 KO mice were confirmed in CX3CR1gfp / gfP knockin mice obtained from Jackson Laboratory (USA). All the mice were housed in colony cages in 12 h light / 12 h dark cycles. For HFD study, 8 week old mice were subjected to NCD or 60% HFD (Research Diets, Inc; USA). For oral glucose tolerance test, the mice were fasted for 6 h and basal blood samples were taken, followed by oral gavage of 2 g / kg bolus glucose. Blood samples were drawn at 10, 20, 30, 45, 60, 90 and 120 min after oral gavage. For intravenial glucose tolerance test, the mice were surgerized for cathether implantation to jugular vein as described previously (Lee et al., 2011). After 3 days of recovery, the mice were fasted for 5 h, and then transferred to restrainers. After 1.5 h of stabilization, blood samples were drawn from tail for basal glucose and insuli...

example 2

CX3CR1-Deficient Mice Exhibit Impaired Glucose Tolerance with Reduced Insulin Secretion

[0072]Obesity causes inflammation and insulin resistance and the FKN / CX3CR1 system plays a role in monocyte attachment and immune cell migration (Combadiere et al., 2003; Hotamisligil et al., 1995; Lee et al., 2010; Lee et al., 2011; Lesnik et al., 2003; Olefsky and Glass, 2010; Tacke et al., 2007; Teupser et al., 2004). To address the potential effect of this receptor on obesity-induced inflammation, lean and obese CX3CR1 KO mice were studied. The KO mice exhibited normal food intake, body weight gain, and liver mass either on chow or high fat diet (HFD) (FIGS. 1A-1C). Adipose tissue mass was the same between KO and WT mice on chow diets, but was slightly lower in the KO mice on HFD (FIG. 1D).

[0073]Interestingly, it was found no evidence that FKN or CX3CR1 play a role in macrophage accumulation in adipose tissue or liver or in inflammation-induced insulin resistance. For example, macrophage infil...

example 3

CX3CR1 KO Islets Display Reduced Insulin Secretion with Decreased Expression of Genes Associated with Beta Cell Function

[0076]To directly test beta cell function, and to determine whether the in vivo insulin secretory defects are primary or secondary, in vitro systems on isolated islets and Min6 cells were carried out. First, to directly test the function of CX3CR1 in beta cells, insulin secretion was measured under static incubation conditions by isolated islets obtained from chow and HFD WT and CX3CR1 KO mice. As seen in FIG. 3A, the KO islets exhibited a marked decrease in GSIS which was more profound in islets obtained from HFD KO mice (FIG. 3B). Moreover, CX3CR1 KO islets exhibited reduced insulin secretion in response to arginine (FIG. 3C), consistent with the in vivo results seen in FIG. 2F. To demonstrate the cell autonomous effects of CX3CR1 on GSIS in another way, and to show that they are independent of in vivo developmental issues, RNAi interference was used to deplete C...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Solubility (mass)aaaaaaaaaa
Levelaaaaaaaaaa
Login to View More

Abstract

Diagnostic, prognostic, and treatment methods, compositions, and kits for enhancing insulin secretion and beta cell numbers and functions, and controlling glycemia associated with diabetes, obesity, atherosclerosis, stroke, myocardial infarction, and other cardiovascular diseases, by modulating FKN / CX3CR1 expression levels or activities, and its downstream signaling pathways in a subject in need or at risk.

Description

CROSS REFERENCES TO RELATED APPLICATIONS[0001]This application is a continuation of PCT Application No. PCT / US2013 / 027860 filed Feb. 27, 2013 which claims priority to U.S. Provisional Application Ser. No. 61 / 605,444 filed on Mar. 1, 2012, the entire contents of which are incorporated by reference herewith.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH[0002]This invention was made with Government support under Grant Nos. DK033651, DK063491, and DK074868 awarded by the National Institutes of Health. The Government has certain rights in the invention.FIELD OF THE INVENTION[0003]The present invention relates to diagnostics and therapeutics for diabetes, atherosclerosis, and other cardiovascular diseases.BACKGROUND OF THE INVENTION[0004]The prevalence of Type 2 diabetes has risen dramatically in the United States and globally and has now reached epidemic proportions (Olefsky and Glass, 2010). The etiology of this disease involves both insulin resistance and decreased beta cell insulin ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K38/19G01N33/68
CPCA61K38/195G01N33/6893G01N2800/042G01N2800/32G01N2333/46A61P3/04A61P3/10A61P5/50A61P9/00A61P9/10A61P43/00G01N33/5091G01N2333/4719G01N2333/52
Inventor OLEFSKY, JERROLD M.LEE, YUN SOK
Owner RGT UNIV OF CALIFORNIA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com