Frequency of mutations of insulin receptor gene in Japanese patients with NIDDM.
AuthorsKan M, Kanai F, Iida M, Jinnouchi H, Todaka M, Imanaka T, Ito K, Nishioka Y, Ohnishi T, Kamohara S
JournalDiabetes
PubMed ID7657032
'To examine the prevalence of abnormalities in the insulin receptor structure gene in Japanese with non-insulin-dependent diabetes mellitus (NIDDM), a population of 51 patients with NIDDM was screened for mutations in this gene. Patient genomic DNAs of both alleles corresponding to 22 exons of the gene were amplified by polymerase ... More
Ligand-induced activation of the insulin receptor: a multi-step process involving structural changes in both the ligand and the receptor.
AuthorsWard CW, Lawrence MC
JournalBioessays
PubMed ID19274663
Current models of insulin binding to the insulin receptor (IR) propose (i) that there are two binding sites on the surface of insulin which engage with two binding sites on the receptor and (ii) that ligand binding involves structural changes in both the ligand and the receptor. Many of the ... More
Insulin degradation: progress and potential.
AuthorsDuckworth WC, Bennett RG, Hamel FG
JournalEndocr Rev
PubMed ID9793760
Insulin degradation is a regulated process that plays a role in controlling insulin action by removing and inactivating the hormone. Abnormalities in insulin clearance and degradation are present in various pathological conditions including type 2 diabetes and obesity and may be important in producing clinical problems. The uptake, processing, and ... More
Substitution of lysine for asparagine at position 15 in the alpha-subunit of the human insulin receptor. A mutation that impairs transport of receptors to the cell surface and decreases the affinity of insulin binding.
AuthorsKadowaki T, Kadowaki H, Accili D, Taylor SI
JournalJ Biol Chem
PubMed ID2121734
Mutations in the insulin receptor gene can compromise the ability of the receptor to mediate insulin action. Previously, in investigations of a patient with a genetic form of insulin resistance, we have identified a mutant allele encoding an insulin receptor in which lysine is substituted for asparagine at position 15 ... More
Genotype-phenotype correlation in inherited severe insulin resistance.
AuthorsLongo N, Wang Y, Smith SA, Langley SD, DiMeglio LA, Giannella-Neto D
JournalHum Mol Genet
PubMed ID12023989
The insulin receptor is a ligand-activated tyrosine kinase. Mutations in the corresponding gene cause the rare inherited insulin-resistant disorders leprechaunism and Rabson-Mendenhall syndrome. Patients with the most severe syndrome, leprechaunism, have growth restriction, altered glucose homeostasis and early death (usually before 1 year of age). Rabson-Mendenhall syndrome is less severe, ... More
Membrane glycoprotein PC-1 inhibition of insulin receptor function occurs via direct interaction with the receptor alpha-subunit.
AuthorsMaddux BA, Goldfine ID
JournalDiabetes
PubMed ID10615944
Plasma cell membrane glycoprotein-1 (PC-1) inhibits insulin receptor (IR) tyrosine kinase activity and subsequent cellular signaling. PC-1 content is elevated in fibroblasts, muscle, and adipose tissue from insulin-resistant subjects, and its elevation correlates with in vivo insulin resistance. In vitro, when PC-1 is transfected and overexpressed in cultured cells, it ... More