Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM
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Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM. / Chen, Y H; Hansen, L; Chen, Min; Bjørbaek, C; Vestergaard, H; Hansen, T; Cohen, Peter; Pedersen, O; Vestergaard, Henrik.
I: Diabetes, Bind 43, Nr. 10, 10.1994, s. 1234-41.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Sequence of the human glycogen-associated regulatory subunit of type 1 protein phosphatase and analysis of its coding region and mRNA level in muscle from patients with NIDDM
AU - Chen, Y H
AU - Hansen, L
AU - Chen, Min
AU - Bjørbaek, C
AU - Vestergaard, H
AU - Hansen, T
AU - Cohen, Peter
AU - Pedersen, O
AU - Vestergaard, Henrik
PY - 1994/10
Y1 - 1994/10
N2 - Impaired insulin-stimulated glycogen synthesis of peripheral tissues is a characteristic feature of many patients with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives with normal glucose tolerance, suggesting putative inherited defects in this metabolic pathway. In previous studies, we have failed to reveal mutations in the coding regions of the muscle-specific glycogen synthase gene and the three genes that encode the catalytic subunits of protein phosphatase 1 (PP1) as frequent causes of insulin resistance. Because the glycogen-associated regulatory subunit of protein phosphatase 1 (PP1 G-subunit) plays a key role in the insulin stimulation of glycogen synthesis and the activity of PP1 is decreased in insulin-resistant subjects, we have now cloned the human G-subunit cDNA to search for abnormalities in the corresponding gene (designated PPP1R3 in the human genome nomenclature) in patients with NIDDM. The human cDNA was isolated from a skeletal muscle cDNA library and was found to encode a 126-kDa protein, which shows 73% amino acid identity to the rabbit PP1 G-subunit. The human G-subunit cDNA from 30 insulin-resistant NIDDM patients was analyzed for genetic variations in the G-subunit by using single-stranded conformation polymorphism (SSCP) scanning of reversely transcribed mRNA. One variant SSCP profile was detected in the region encoding the COOH-terminal part of the PP1 G-subunit in only one NIDDM patient, and subsequent nucleotide sequencing showed a C to A transversion on one allele at base position 2792. This change predicts an amino acid substitution from alanine to glutamic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
AB - Impaired insulin-stimulated glycogen synthesis of peripheral tissues is a characteristic feature of many patients with non-insulin-dependent diabetes mellitus (NIDDM) and their first-degree relatives with normal glucose tolerance, suggesting putative inherited defects in this metabolic pathway. In previous studies, we have failed to reveal mutations in the coding regions of the muscle-specific glycogen synthase gene and the three genes that encode the catalytic subunits of protein phosphatase 1 (PP1) as frequent causes of insulin resistance. Because the glycogen-associated regulatory subunit of protein phosphatase 1 (PP1 G-subunit) plays a key role in the insulin stimulation of glycogen synthesis and the activity of PP1 is decreased in insulin-resistant subjects, we have now cloned the human G-subunit cDNA to search for abnormalities in the corresponding gene (designated PPP1R3 in the human genome nomenclature) in patients with NIDDM. The human cDNA was isolated from a skeletal muscle cDNA library and was found to encode a 126-kDa protein, which shows 73% amino acid identity to the rabbit PP1 G-subunit. The human G-subunit cDNA from 30 insulin-resistant NIDDM patients was analyzed for genetic variations in the G-subunit by using single-stranded conformation polymorphism (SSCP) scanning of reversely transcribed mRNA. One variant SSCP profile was detected in the region encoding the COOH-terminal part of the PP1 G-subunit in only one NIDDM patient, and subsequent nucleotide sequencing showed a C to A transversion on one allele at base position 2792. This change predicts an amino acid substitution from alanine to glutamic acid.(ABSTRACT TRUNCATED AT 250 WORDS)
KW - Amino Acid Sequence
KW - Animals
KW - Base Sequence
KW - DNA Primers
KW - Diabetes Mellitus, Type 2
KW - Female
KW - Glucose
KW - Glycogen
KW - Humans
KW - Macromolecular Substances
KW - Male
KW - Middle Aged
KW - Molecular Sequence Data
KW - Muscles
KW - Phosphoprotein Phosphatases
KW - Polymerase Chain Reaction
KW - Polymorphism, Genetic
KW - Protein Phosphatase 1
KW - RNA, Messenger
KW - Rabbits
KW - Reference Values
KW - Sequence Homology, Amino Acid
M3 - Journal article
C2 - 7926294
VL - 43
SP - 1234
EP - 1241
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 10
ER -
ID: 92193678