Genetic analysis of human type 1 protein phosphatase inhibitor 2 in insulin-resistant Pima Indians.
The rate-limiting enzyme in insulin-mediated nonoxidative glucose disposal, glycogen synthase, has reduced activity in insulin-resistant subjects at risk for developing non-insulin-dependent diabetes mellitus (NIDDM). The synthase-activating enzyme, type 1 protein phosphatase (PP1), also has an abnormally low level of activity. Inhibitor 2 (I-2) reversibly inhibits and facilitates the proper conformation of free catalytic subunits of PP1. This study investigates whether genetic alteration(s) in the I-2 coding locus (PPP1R2) could contribute to insulin resistance in Pima Indians. We determined that the authentic PPP1R2 gene is located on chromosome 3q29 and consists of six exons. The previously reported homologue of PPP1R2 on chromosome 5 is identified as an intronless pseudogene. Comparative sequencing of PPP1R2 exons and splice junctions revealed no mutations in insulin-resistant Pima Indians. The information on the genomic structure of PPP1R2 is important for exploring this gene as a potential candidate contributing to insulin resistance and NIDDM in other populations.
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Clinical Diabetes and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona 85016, USA.
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D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004791:Enzyme Inhibitors / Q000378:metabolism; D005091:Exons; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D007438:Introns; D008969:Molecular Sequence Data; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D011506:Proteins / Q000235:genetics*; D011544:Pseudogenes; D000097847:Protein Phosphatase Inhibitory Proteins
D017931:DNA Primers; D004791:Enzyme Inhibitors; D010749:Phosphoprotein Phosphatases; D011506:Proteins; C024833:protein phosphatase inhibitor-2; D000097847:Protein Phosphatase Inhibitory Proteins