Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus
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Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus. / Hansen, Torben; Bjørbaek, C; Vestergaard, H; Grønskov, K; Bak, J F; Pedersen, O.
I: The Journal of clinical endocrinology and metabolism, Bind 77, Nr. 6, 12.1993, s. 1500-5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › fagfællebedømt
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TY - JOUR
T1 - Expression of insulin receptor spliced variants and their functional correlates in muscle from patients with non-insulin-dependent diabetes mellitus
AU - Hansen, Torben
AU - Bjørbaek, C
AU - Vestergaard, H
AU - Grønskov, K
AU - Bak, J F
AU - Pedersen, O
PY - 1993/12
Y1 - 1993/12
N2 - Due to alternative splicing of exon 11 of the receptor gene, the human insulin receptor exists in two forms, that have distinct tissue-specific expression and are functionally different. Needle biopsies obtained from vastus lateralis muscle from 20 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 20 normal control subjects were analyzed for the relative expression of insulin receptor mRNA variants in a novel assay using fluorescence-labeled primers and subsequent analysis on an automated DNA sequencer. In subgroups of patients and control subjects, insulin binding and tyrosine kinase activity were examined in wheat germ agglutinin-purified insulin receptors isolated from muscle biopsies. Moreover, insulin-stimulated glucose disposal was studied by means of the euglycemic hyperinsulinemic clamp technique. No difference in the relative expression of spliced variants of the insulin receptor mRNA was observed (control subjects, 71.4 +/- 1.3% insulin receptor mRNA with exon 11; NIDDM patients, 71.5 +/- 1.3% insulin receptor mRNA with exon 11). No significant interrelationships were demonstrated among the relative expression of insulin receptor mRNA variants, insulin binding, and tyrosine kinase activity toward the exogenous substrate poly(Glu-Tyr(4:1)). Furthermore, no significant relationship was demonstrated between the glucose disposal rate and the relative expression of insulin receptor splice variants. In conclusion, in skeletal muscle from both normal control subjects and NIDDM patients, the proportion of insulin receptor mRNA with exon 11 is about 70%. In addition, no significant correlations exist among insulin binding, insulin receptor tyrosine kinase activity, glucose disposal rate, and expression of alternative spliced insulin receptors in human skeletal muscle.
AB - Due to alternative splicing of exon 11 of the receptor gene, the human insulin receptor exists in two forms, that have distinct tissue-specific expression and are functionally different. Needle biopsies obtained from vastus lateralis muscle from 20 patients with noninsulin-dependent diabetes mellitus (NIDDM) and 20 normal control subjects were analyzed for the relative expression of insulin receptor mRNA variants in a novel assay using fluorescence-labeled primers and subsequent analysis on an automated DNA sequencer. In subgroups of patients and control subjects, insulin binding and tyrosine kinase activity were examined in wheat germ agglutinin-purified insulin receptors isolated from muscle biopsies. Moreover, insulin-stimulated glucose disposal was studied by means of the euglycemic hyperinsulinemic clamp technique. No difference in the relative expression of spliced variants of the insulin receptor mRNA was observed (control subjects, 71.4 +/- 1.3% insulin receptor mRNA with exon 11; NIDDM patients, 71.5 +/- 1.3% insulin receptor mRNA with exon 11). No significant interrelationships were demonstrated among the relative expression of insulin receptor mRNA variants, insulin binding, and tyrosine kinase activity toward the exogenous substrate poly(Glu-Tyr(4:1)). Furthermore, no significant relationship was demonstrated between the glucose disposal rate and the relative expression of insulin receptor splice variants. In conclusion, in skeletal muscle from both normal control subjects and NIDDM patients, the proportion of insulin receptor mRNA with exon 11 is about 70%. In addition, no significant correlations exist among insulin binding, insulin receptor tyrosine kinase activity, glucose disposal rate, and expression of alternative spliced insulin receptors in human skeletal muscle.
KW - Adult
KW - Aged
KW - Alternative Splicing
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Humans
KW - Male
KW - Middle Aged
KW - Muscles
KW - Polymerase Chain Reaction
KW - RNA, Messenger
KW - Receptor, Insulin
M3 - Journal article
C2 - 8263133
VL - 77
SP - 1500
EP - 1505
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 6
ER -
ID: 92194060