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The distribution of insulin signalling proteins in human adipose tissue in polycystic ovary syndrome and type 2 diabetes mellitus
Başlık:
The distribution of insulin signalling proteins in human adipose tissue in polycystic ovary syndrome and type 2 diabetes mellitus
Yazar:
Jones, Christopher Jonathan, author.
ISBN:
9780438059344
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (169 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 76-08C.
Advisors: John Connell.
Özet:
Insulin resistance reflects a fundamental defect underlying the conditions of type 2 diabetes mellitus and polycystic ovary syndrome (PCOS). Impaired translocation of the glucose transporter GLUT-4 in response to insulin, results in reduced glucose uptake (a defining feature of insulin resistance). Evidence suggests that at least two independent insulin signalling pathways must co-exist and function normally to allow full insulin stimulated glucose uptake. One such pathway may involve specialised areas of the lipid membrane, known as lipid rafts, which contain proteins necessary for the docking and fusion of GLUT-4 containing vesicles. The importance of adipose tissue in the development of insulin resistance has been clearly demonstrated. This thesis describes studies of insulin signalling pathways in adipose tissue of patients with type 2 diabetes mellitus and polycystic ovary syndrome. Study outline: 13 patients with type 2 diabetes mellitus, 7 with PCOS and 13 control subjects were recruited to the study. Measurement of insulin sensitivity using the isoglycaemic hyperinsulinaemic glucose clamp technique was performed. Samples of adipose tissue were obtained by gluteal biopsy. Adipose tissue then underwent a subcellular fractionation process. Total concentration and the subcellular localisation of proteins were examined using a western blotting process. Results: There was wide variation in the total protein content of adipose tissue samples. This is likely to be due to a low yield of protein from relatively small, highly lipid laden adipose tissue samples. The subcellular fractionation process yielded membrane fractions too small to examine in a number of subjects and introduced further variation. No statistically significant data was gained due to low sample size and high variation. However, the total expression of Caveolin-1 appeared to be reduced and the total expression of TC-10 and VAMP-2 increased. Conclusion: No conclusions regarding the total expression or subcellular localisation of insulin signalling proteins were gained. Improved recruitment and larger samples of adipose tissue using an alternative method, may give larger proteins yields resulting in less variability. It is interesting to observe that the expression of caveolin-1 may be reduced in the type 2 diabetes group, contradicting observations in an animal model of insulin resistance. However, the protein TC-10 may be over-expressed in type 2 diabetes mellitus, perhaps as an adaptive response or adversely influencing downstream effectors. The vSNARE protein, VAMP2, may show an over-expression in type 2 diabetes mellitus, mirroring similar observations seen in animal model, perhaps resulting in impaired spatial distribution of other SNARE proteins within lipid membrane microdomains.
Notlar:
School code: 0547
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(684711.1) | 684711-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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