Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving nucleic acid
Patent
1994-11-21
1998-02-17
Jones, W. Gary
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving nucleic acid
435 912, 536 231, 536 243, 536 2433, C12Q 168, C12P 1934, C07H 2102, C07H 2104
Patent
active
057190224
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 application of PCT/EP 92/00949 filed Apr. 30, 1992.
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention concerns a process for the diagnosis of nondiabetes mellitus or a genetically conditioned disposition to it.
2. Description of the Prior Art
Type 2 diabetes (noninsulin-dependent diabetes mellitus, NIDDM) has strongly increased in the population in recent decades. There is, therefore, a great interest in providing an easily implemented possibility for diagnosing this diabetes early or, if possible, to be able to detect a genetically conditioned disposition to it before the actual outbreak of the disease.
The task of the present invention was to prepare a process for this that makes it possible to determine rapidly and precisely whether the genetic basis for the disease is present in a patient.
This task was solved by the process according to the invention for diagnosing noninsulin-dependent diabetes mellitus or a genetically determined disposition to it, in which we test cells, especially skeletal muscle cells, of patients for the presence of type B human insulin receptors (HIR-B).
The process according to the invention is based on the surprising recognition that very specific differences can be detected in the presence of the two forms of insulin receptors (HIR-A, HIR-B) in the cells of diabetics in comparison with healthy persons.
Both forms of the receptors have been known for a long time, and research on them has been described by von Mosthaf et al., EMBO Journal, vol. 9, No. 8, pp 2409-2413 (1990) as well as in earlier literature referred to there, especially Ebina et al., Proc. Natl. Acad. Sci. USA 84 (1987), pp. 704-708; Ullrich et al.,
Nature 313 (1985), pp. 756-761; S. Seino and F. I. Bell, Biochem. Biophys. Res. Common. 159 (1989), pp. 312-316), and Y. Yarden and A. Ullrich, Annu. Rev. Biochem. 57 (1988), pp. 443-478. It was established in them that there are two different forms of receptors, called A and B, both of which consist of equal .alpha. and .beta. subunits connected with disulfide bonds, where there is a difference, however, in that the type B .alpha. subunits have an insertion of 12 amino acids in the region of the C terminal. Since only a single gone can be identified for an insulin receptor, the suspicion was close at hand that a posttranscriptional mechanism is involved in the origin of the two different forms, A and B. Is was further established that the 12 amino acid insert of the B form is coded by a separate exon, and both forms arise from alternative splicing of the primary transcript. It was also established in this regard that the presence of HIR-A and HIR-B RNA depends, both as to amount and in principle, on the tissue. It was also found that the two receptor forms have different binding characteristics for insulin.
SUMMARY OF THE INVENTION
In the framework of the present invention, it has now been established that especially in skeletal muscles, but also in other types of tissue cells, there is specifically in NIDDM patients or persons with a genetically conditioned disposition to it, a nearly equal amount of type A and type B of the human insulin receptor, while in healthy people, only type A receptors are found in the same cells. This is in contrast to some other types of cells in which both receptor types can exist even in healthy people, as can be seen from the literature cited above. In contrast to tissue cells, for example, in human blood cells there is no apparent difference between nondiabetic persons and NIDDM patients. In both cases, there are only type A receptors present, while type B receptors cannot be detected.
In the process according to the invention, all methods can be used in principle that permit a distinction to be made between the two receptor types. Tissue cells for this can be obtained in a known manner, especially by biopsy of patients.
In a preferred implementation of the process according to the invention, we proceed in such a manner that the test for the presence of type B receptors in skeletal mu
REFERENCES:
patent: 4965189 (1990-10-01), Owerbach
Mosthof et al. EMBO J. 9: 2409-2413, 1990.
Mosthof et al. PNAS 88: 4728-4730, 1991.
Seino et al. Biochemical and Biophysical Research Communications 159: 3126, 1989.
Ullrich et al. Nature 313: 756-761, 1985.
Haring Hans-U.
Seedorf Luitgard
Ullrich Axel
Jones W. Gary
Max-Planck-Gesellschaft zur Forderung der Wissenschaften e.v.
Rees Dianne
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