Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Total polyadenylated RNA prepared from isolated islets of fetal bovine pancreas was physically characterized. Incubation of this poly A+ RNA with a cell-free protein-synthesizing system derived from wheat germ results in the synthesis of insulin-immunoreactive polypeptide identical in size to that described earlier, 11 200 daltons (Lomedico et al. (1977) J. Biol. Chem. 252, 7971--7978). This material comprised approximately 22% of the total 3H-labeled translation products. Compared to poly A+ RNA from the total pancreas, we conclude that islet mRNA is enriched in proinsulin mRNA.
Mol Cell Endocrinol 1979 Aug
PMID:Isolation and characterization of preproinsulin mRNA from fetal bovine pancreatic islets. 38 99

Insulin binding was demonstrated in cultured HT 29 cells originating from a human colon carcinoma. At 37 degrees and in complete medium, the binding of [125I]insulin (1-4x10-10M) reaches a maximum in 40 min and the cell associated radioactivity remains constant for at least 4 h. No degradation of the hormone is observed under these conditions. The binding is proportional to the number of cells and its pH optimum is 7.8. In the presence of excess insulin 50% of the [125I]insulin is dissociated from the complex after 10 min. At equilibrium, insulin binding is specific: proinsulin is 25 times less potent than native insulin in competing with [125I]insulin and related polypeptide hormones are inactive. Scatchard analysis indicates two classes of binding sites (1400 sites/cell of "high affinity" e.g. 4.7 x 108 M-1, and 20 000 sites of "low affinity" e.g. 4 x 107 M-1). The binding of insulin to this non-target cell shows the same kinetic characteristics and specificity as found for insulin in its target cells, except that HT 29 cells do not degrade the hormone. The problem of the correlation between insulin binding and a biological effect in these cells remains to be elucidated.
Mol Cell Endocrinol 1979 May
PMID:Insulin binding by a cell line (HT 29) derived from human colonic cancer. 46 79

1. Glucose-infusion tests were performed on patients admitted for elective upper abdominal surgery 1 day before and 1 day after operation. In addition to insulin and proinsulin, a third immunoreactive insulin species of mol. wt. 20 000--30 000 was detected in plasma from two patients. The heterogeneity of plasma immunoreactive insulin (IRI) and the need to consider the effects of all forms, including proinsulin and the high-molecular-weight species, is emphasized. 2. During preoperative glucose infusions there was an increase in the percentage of the total plasma IRI present as high-molecular-weight forms (i.e. proinsulin plus the species of mol. wt. 20 000--30 000) from 3.9% to 10.8%. On the first postoperative morning all patients showed an increase in the amounts of the heavier IRI types, which accounted for 13.9% of the total plasma IRI. 3. The changes in insulin and proinsulin are consistent with the release from the pancreas of an insulin/proinsulin mixture of constant proportions, and the longer circulating half-life of proinsulin. 4. Increases in the amounts of high-molecular-weight IRI species after surgery may have a partial role in the development of insulin resistance but are probably not a major determinant of the insulin-resistant state.
Clin Sci Mol Med 1977 Dec
PMID:Changes in the proportions of plasma insulin, proinsulin and a higher-molecular-weight insulin during pre- and post-operative glucose-infusion tests. 58 39

The codons in four mammalian messenger RNAs (rabbit beta hemoglobin, rat pre-proinsulin, rat pre-growth hormone and human chorionic somatomammotropin) show a predominance of C and G in third nucleotide positions. The C:U ratio is about 2 to 1, and the G:A ratio is about 4 to 1. The possibility is discussed that this disproportionally resulted from DNA replicative errors that favor C.G pairs over A.T pairs, as found in the E. coli mut T strain. "Nearest neighbor" base pairs ("doublets") in the protein-coding regions of phiX174 and in four mammalian mRNAs have been compared. Mammalian mRNA has a low content of CpG in comparison with expectations from its C and G content.
J Mol Evol 1978 Jun 20
PMID:Codons and nearest-neighbor nucleotide pairs in mammalian messenger RNA. 67 60

An analysis is made of the applicability of the recently published 'profiles of relationship' method for establishing evolutionary relatedness among proteins by using the distantly related proinsulin and neurotoxin protein sequences as a test object. The method is based on a simultaneous group analysis of both the frequency of acceptance of mutations and their genetic code interchangeability. Regularities in the patterns of the profiles, which reflect decreased similarity with the passage of time, are established for typical cases of closely related, distantly related and unrelated proteins. This makes it possible to distinguish distantly related from unrelated proteins without extensive statistical randomization procedures. New evidence is stated in favour of a previously suggested definition of interchangeability which does not consider the third base in the codon. The applicability of the profiles of relationship method is examined on the distant relationship between proinsulin and the snake and scorpion neurotoxins which has been established previously by means of conventional approaches.
J Mol Evol 1978 Oct 27
PMID:Application of the 'profiles of relationship' method to distantly related proteins. 73 7

Human C-peptide is determined by radioimmunoassay. On gel filtration of serum from a healthy subject and from a patient with islet cell carcinoma, C-peptide (MW 3025) appears ahead of insulin (MW 5808) and shows much higher molar concentrations than the hormone. Human proinsulin cross-reacts with our antiserum to synthetic human C-peptide. On direct determination of immunomeasurable C-peptide (IMCP) in fasting serum of 25 healthy subjects we find an average of 1.8 (+/- 0.4) ng/ml, corresponding to 60.4 X 10(-11) Mol/l. The molar concentration is about five-fold as compared to IMI (immuno-measurable insulin). IMCP and IMI patterns are not identical on stimulation of beta-cell secretion in healthy subjects by i.v. glucose or glucose-glibenclamide. This is probably due to differences in peripheral metabolism of both compounds. We conclude from our results that C-peptide determined in peripheral venous serum is a better indicator of beta-cell secretion than is insulin. Among 26 insulin-treated juvenile diabetics 15 show not measurable and 11 subnormal IMCP levels in fasting serum. No rise in IMCP is found 1-2 h following breakfast. Four juvenile patients receiving no insulin in a phase of total diabetes remission have normal or raised fasting IMCP concentrations. Only 2 out of 24 adult diabetics (16 treated with insulin and 8 with tablets) show non-measurable fasting IMCP concentrations, in another 4 patients values are below and in the remaining 18 cases above 1 ng/ml serum. Stimulation of beta-cell secretion through glucose-glibenclamide is more or less impaired in all adult diabetics compared to the healthy subjects.
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PMID:Human C-peptide. Part II: Clinical studies. 82 96

An analysis of primary structures for local similarities has been performed for a number of protein hormones. The statistical MacLachlan's technique and three matrices of amino acids similarities: in respect to the genetic code (M1), physico-chemical properties (M2), interchangeability of amino acids in homologous proteins (M3) have been used. When comparing prolactin and growth hormones, four zones of high structural similarity have been found. Comparison of beta-subunits of interstitial-cell and thyroid-stimulating hormones has shown two zones of high similarity. Using M3 matrice, non-homogeneity of the self local similarity of structure has been shown for prolactin, growth hormone, beta-lipotropin, proinsulin and parathormone. For the latter three hormones, the high evolutionary conservative regions coincide with the active sites of structure. It is suggested that such regions in the structures of prolactin and growth hormone also provide the active function.
Mol Biol (Mosk)
PMID:[An analysis of local similarities in the primary structures of protein hormones]. 94 64

The distribution of proinsulin and insulin immunoreactivity was studied in 76 human insulinomas and in normal pancreas. One trabecular and two solid insulinomas showed the staining pattern of normal beta cells. A "near normal" staining pattern (perinuclear proinsulin and diffuse or polarized insulin staining) existed in 10 of 27 trabecular and 11 of 44 solid insulinomas. An "intermediate" staining pattern (intense perinuclear as well as weaker diffuse proinsulin staining with diffuse or polarized insulin staining) was observed in 10 of 27 trabecular and 20 of 44 solid insulinomas. Different "abnormal" staining patterns were found in 6 of 27 trabecular and 6 of 44 solid insulinomas. Of the 5 glandular insulinomas, 4 exhibited a "near normal" and one an "abnormal" staining pattern. No correlation was found between any particular staining pattern and the multihormonality or malignancy of the insulinomas. The diffuse labeling for proinsulin in about 50% of the insulinomas is suggestive of abnormal prohormone processing.
Virchows Arch B Cell Pathol Incl Mol Pathol 1992
PMID:Distribution patterns of proinsulin and insulin in human insulinomas: an immunohistochemical analysis in 76 tumors. 136 22

Insulin-like growth factors (IGFs) are polypeptide hormones with structural homology to proinsulin. IGFs circulate in blood bound to specific IGF binding proteins (IGFBPs). cDNA sequences of six members of a family of human and rat IGFBPs have been published. Here we present a partial characterization of the human IGFBP-2 gene. This single copy gene is located on chromosome 2 and spans a total of more than 32 kilobases (kb) of genomic sequence. It is organized in four exons with sizes of more than 568, 220, 141, and 496 nucleotides. The intron between exon one and exon two contributes 27 kb to the size of the IGFBP-2 gene. The second and the third introns comprise 1.1 kb and 1.95 kb, respectively. When the structure of the IGFBP-2 gene is compared to that of the IGFBP-1 and IGFBP-3 genes, the exon boundaries are found to be conserved in these three genes. A single transcriptional start site was localized to 113 +/- 2 nucleotides 5' of the ATG start codon of IGFBP-2 translation. Furthermore, the region between nucleotides -635 and -2 upstream of the ATG was demonstrated to exhibit promoter activity in human Jurkat K16 cells. This region is devoid of TATA or CAAT consensus sequence motifs and has a high content of dC and dG nucleotides. In this respect the putative IGFBP-2 promoter region resembles the promoters which are often associated with housekeeping genes.
Mol Endocrinol 1992 May
PMID:Structure of the human insulin-like growth factor binding protein-2 gene. 137 11

Glucagon-like peptide-1 (GLP-1) is the main product of the intestinal processing of proglucagon. It is released from the intestinal K-cells into the circulation in response to the oral ingestion of food. At the pancreatic beta cell GLP-1 is a potent insulin secretagogue in the presence of elevated glucose levels, defining glucagon-like peptide-1 as a new incretin. Its action is mediated by specific receptors coupled to the adenylate cyclase system by a stimulatory G-protein. Finally, glucagon-like peptide-1 stimulates proinsulin gene expression and it is thus involved at several levels in the regulation of insulin synthesis and secretion.
Mol Cell Endocrinol 1992 May
PMID:Glucagon-like peptide-1(7-37)/(7-36)amide is a new incretin. 138 25


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