Compositions and methods for diagnosis and treatment of type 2 diabetes

Inactive Publication Date: 2009-08-13
AMERICAN TYPE CULTURE COLLECTION
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0010]The present invention is premised on the discovery that disease-associated biomarkers can be identified in serum or other bodily fluids long before overt disease is apparent. The presence or absence of these biomarkers from the serum footprints of patients suffering from Type 2 Diabetes precede disruptions in blood glucose control and can be used as early diagnostic tools, for which treatment strategies can be devised and administered to prevent, delay, ameliorate, or reverse irreversible organ damage. One or several of the disease-associated bi

Problems solved by technology

Symptoms include increased thirst and urination, hunger, weight loss, chronic infections, slow wound healing, fatigue, and blurred vision.
Often, however, symptoms are not severe, not recognized, or are absent.
Diabetes can lead to debilitating and life-threatening complications including retinopathy leading to blindness, memory loss, nephropathy that may lead to renal failure, cardiovascular disease, neurop

Method used

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  • Compositions and methods for diagnosis and treatment of type 2 diabetes
  • Compositions and methods for diagnosis and treatment of type 2 diabetes
  • Compositions and methods for diagnosis and treatment of type 2 diabetes

Examples

Experimental program
Comparison scheme
Effect test

example 1

Biomarker Identification in the Cohen Rat Model of Type 2 Diabetes

[0247]The Cohen diabetic (CD) rat is a well-known and versatile animal model of Type 2 Diabetes, and is comprised of 2 rodent strains that manifest many of the common features of Type 2 Diabetes (T2D) in humans. The sensitive strain (CDs) develops Diabetes within 30 days when maintained on a high sucrose / copper-poor diet (HSD), whereas the resistant strain (CDr) retains normal blood glucose levels. When maintained indefinitely on regular rodent diet (RD), neither strain develop symptoms of T2D.

Sample Preparation

[0248]Serum, urine, and tissue samples (including splenic tissue, pancreatic tissue, and liver tissue) were obtained from both CDr and CDs rats that were fed either RD or HSD for 30 days. The samples were flash-frozen and stored at −80° C.

[0249]Whole protein extracts were prepared for each of the 4 experimental conditions, utilizing 10 individual organs per group. Pancreatic tissues were processing using a mech...

example 2

Bi-Directional Immunological Contrasting and Generation of Monoclonal Antibodies

[0268]From the pancreatic extract protein profiles obtained by SDS-PAGE, obvious differences in the banding patterns were noted between CDr-HSD and CDs-HSD samples. Bi-directional immunological contrast was performed between these two samples. This technique involves injecting two pancreatic extracts from the Cohen diabetic rats to be contrasted separately into the footpads of an experimental animal (e.g. a Balb / c mouse). Following uptake and processing of the antigen at the site of injection by antigen presenting cells (APCs), the activated APCs migrate to the local lymph nodes (popliteal) to initiate an immune response. As these lymph nodes are located in each leg, they are anatomically separated from each other, which prevents mixing of antigen-specific lymphocytes at this point. Later in the immune response, these activated lymphocytes migrate from the local lymph nodes to the spleen where they becom...

example 3

Microarray Analysis of Gene Expression in Tissues from Cohen Type 2 Diabetic Rats

[0285]The microarray data were analyzed through Phase I and Phase II analyses. Phase I is based on the processed data from Gene Logic. Phase II corresponds to data analysis using GeneSpring GX. Additional criteria including statistics, signaling pathways and clustering were used for the analyses.

[0286]The microarray results from Gene Logic (Phase I) that were derived from comparisons of pancreatic total RNA of Cohen Type 2 Diabetes rats (CDs-HSD, CDr-HSD) were analyzed using MAS5.0 software from Affymetrix, Inc. The global gene expression analysis showed that there were 1178 genes upregulated in CDr-HSD and 803 genes were downregulated in compared to CDs-HSD. Many of these transcripts are involved in several signaling pathways related to Type 2 Diabetes such as insulin signaling, beta-cell dysfunction and lipid and glucose metabolisms. Also, several serpin family members (serine proteinase inhibitors) a...

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Abstract

The present invention relates generally to the identification of biological markers associated with an increased risk of developing Diabetes, as well as methods of using such biological markers in diagnosis and prognosis of Diabetes. The biological markers of the invention may indicate new targets for therapy or constitute new therapeutics for the treatment or prevention of Diabetes.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of U.S. application Ser. No. 11 / 901,925, filed on Sep. 18, 2007, which is a continuation-in-part of International Application No. PCT / US2007 / 007875, filed on Mar. 28, 2007, which claims priority from U.S. Provisional Application Ser. No. 60 / 841,717, filed on Sep. 1, 2006.[0002]Each of the applications and patents cited in this text, as well as each document or reference cited in each of the applications and patents (including during the prosecution of each issued patent; “application cited documents”), and each of the U.S. and foreign applications or patents corresponding to and / or claiming priority from any of these applications and patents, and each of the documents cited or referenced in each of the application cited documents, are hereby expressly incorporated herein by reference. More generally, documents or references are cited in this text, either in a Reference List before the claims, or ...

Claims

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Application Information

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IPC IPC(8): A61K38/17C07K14/47C12N15/12C12N9/99A61P3/10
CPCC12Q1/6883C12Q2600/118C12Q2600/158A61P3/10
Inventor GELBER, COHAVALIU, LIPINGXIE, ZHIDONGIKONOMI, PRANVERASIMMS, JOHN R.AUGE, CATHERINE R.
Owner AMERICAN TYPE CULTURE COLLECTION
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