Abstract | OBJECTIVE: RESULTS: In the fibroblasts from pseudo-acromegalic insulin resistant subjects PC-1 activity and PC-1 protein and mRNA levels were indistinguishable from the normoinsulinaemic controls. Consistent with this observation, insulin receptor tyrosine kinase activity was similar in extracts from fibroblasts of pseudo-acromegalic subjects and normal controls. Surprisingly, subjects with insulin receptor or IRS-1 mutations had a profound reduction in PC-1 activity (p < or = 0.005), protein (p < or = 0.05) and mRNA levels (P < or = 0.005). CONCLUSIONS: The results indicate that PC-1 over-expression does not appear to contribute to the insulin resistant state of pseudo-acromegalic patients. The finding of normal insulin receptor tyrosine kinase activity in these subjects suggests that the site of defective insulin signalling is likely to be distal to the receptor. The unexpected finding that PC-1 activity, protein and mRNA were all dramatically reduced in patients with lesions early in the insulin signalling cascade provides further evidence for a link, albeit as yet poorly understood, between cellular insulin action and the expression of PC-1.
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Authors | J P Whitehead, P J Humphreys, K Dib, J W Goding, S O'Rahilly |
Journal | Clinical endocrinology
(Clin Endocrinol (Oxf))
Vol. 47
Issue 1
Pg. 65-70
(Jul 1997)
ISSN: 0300-0664 [Print] England |
PMID | 9302374
(Publication Type: Journal Article)
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Chemical References |
- Membrane Glycoproteins
- RNA, Messenger
- Receptor, Insulin
- Phosphoric Diester Hydrolases
- ectonucleotide pyrophosphatase phosphodiesterase 1
- Pyrophosphatases
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Topics |
- Cells, Cultured
- Fibroblasts
(metabolism)
- Humans
- Insulin Resistance
(physiology)
- Membrane Glycoproteins
(analysis, genetics, metabolism)
- Phosphoric Diester Hydrolases
(metabolism)
- Phosphorylation
- Pyrophosphatases
- RNA, Messenger
(analysis)
- Receptor, Insulin
(antagonists & inhibitors)
- Skin
(metabolism)
- Syndrome
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