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Areas of activity:
-  Medicine, Human Health 
  
 1) Technology Offer
Method to determine proinsulin and C-peptide in serum for diabetes screening 
 
ABSTRACT:
The present invention relates to methods to determine the concentrations of proinsulin and of C-peptide in a sample and to kits for use in such methods, useful in diabetes screening. A generalized equivalent of the above method may be useful in any situation in which the concentrations in a sample need to be determined for two or more analytes, all of which comprise a common portion, and each of which, or each of which except one, comprises a distinct specific portion.

DESCRIPTION:
The pancreatic peptide hormone insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. In response to extracellular stimuli like glucose or glucagon, insulin is produced in beta cells of the islets of Langerhans from preproinsulin, which is rapidly transformed into proinsulin. Proinsulin contains the A and B chains of insulin, joined by a connecting C-peptide. Proinsulin is converted to mature insulin by removal of the C-peptide in nascent secretary granules. This conversion is achieved to a large extent before secretion. Insulin and C-peptide are secreted in equimolar quantities when beta granules fuse with the plasma membrane.
Circulating levels of proinsulin, insulin and C-peptide depend on the rate of secretion into the blood stream and clearance from it. Based on the short half life of insulin in the body (4 min) compared to that of proinsulin and C-peptide (approximately 30 min), the ratio of proinsulin to C-peptide may be considered as a more stable parameter than the proinsulin/insulin ratio. Further, It functions as a marker for the functional state of the pancreatic beta cells and studies in different patient groups show that the proinsulin/C-peptide ratio might be a predictive marker for diabetes development, especially in the short term period before onset. This notion is confirmed by the observation of statistically significant differences in the proinsulin/C-peptide ratio between populations of individuals having distinct clinical pictures or distinct risks for developing a disease. However, there remains a considerable overlap in individual proinsulin/C-peptide ratios between such different populations when measured with current techniques. This limits the application of the proinsulin/C-peptide ratio as a predictive marker in individual prognosis.
The overlap may be partially caused by analytical errors inherent to the current methods of determining the ratio. Up till now, ratios are estimated from concentrations of proinsulin, C-peptide or insulin, respectively, which are measured by separate immunoassay methods, performed in separate reaction compartments. In such case, the analytical errors of the separate methods cumulate when determining the ratio. An aim of the present invention is therefore to provide an improved method that allows determining the proinsulin/C-peptide ratio or proinsulin/insulin ratio with higher precision than can be achieved by currently available approaches.
The present invention provides a method to determine the concentrations in a sample of proinsulin and of molecules comprising C-peptide, wherein the concentrations are determined within the same reaction compartment and using a common capture antibody specific for an epitope within C-peptide. However, as proinsulin comprises the entire sequence of C-peptide and C-peptide does not comprise any portion which is not present in proinsulin, it is impossible to distinguish C-peptide from proinsulin using a distinct detection antibody. Therefore the concentration of C-peptide in these samples may be determined by subtracting the concentration of proinsulin from the concentration of all molecules comprising C-peptide. The proinsulin/C-peptide ratio can then be readily computed.
A generalized equivalent of the above method may be useful in any situation in which the concentrations in a sample need to be determined for two or more analytes, all of which comprise a common portion, and each of which, or each of which except one, comprises a distinct specific portion.


INNOVATIVE ASPECTS:

MAIN ADVANTADGES / BENEFITS:

TECHNICAL SPECIFICATIONS:

CURRENT STAGE OF DEVELOPMENT:

INTELLECTUAL PROPERTY RIGHTS (IPR): Patent pending

MARKET APPLICATIONS: Human Health, endocrinology, screening,

TYPE OF COLLABORATION SOUGHT: Licensing, technical cooperation

PARTNER PROFILE: 
 
Market application:
-  Health issue diagnosis
-  Other human health related topics 
Further commentsDiabetes (proinsulin levels/Cpeptide screening)
Diagnosis/screening tools (general: screening of two or more analytes (peptides) with common and specific portion.) 
  
Entry/Update:2006-12-13  /  2007-02-15

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