Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MicroRNAs (miRNAs) constitute a growing class of non-coding RNAs that are thought to regulate gene expression by translational repression. Several miRNAs in animals exhibit tissue-specific or developmental-stage-specific expression, indicating that they could play important roles in many biological processes. To study the role of miRNAs in pancreatic endocrine cells we cloned and identified a novel, evolutionarily conserved and islet-specific miRNA (miR-375). Here we show that overexpression of miR-375 suppressed glucose-induced insulin secretion, and conversely, inhibition of endogenous miR-375 function enhanced insulin secretion. The mechanism by which secretion is modified by miR-375 is independent of changes in glucose metabolism or intracellular Ca2+-signalling but correlated with a direct effect on insulin exocytosis. Myotrophin (Mtpn) was predicted to be and validated as a target of miR-375. Inhibition of Mtpn by small interfering (si)RNA mimicked the effects of miR-375 on glucose-stimulated insulin secretion and exocytosis. Thus, miR-375 is a regulator of insulin secretion and may thereby constitute a novel pharmacological target for the treatment of diabetes.
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PMID:A pancreatic islet-specific microRNA regulates insulin secretion. 1553 71

Mecasermin (recombinant human insulin-like growth factor-I [IGF-I]) is approved in the US for the long-term treatment of growth failure in children with severe primary IGF-I deficiency or with growth hormone (GH) gene deletion who have developed neutralizing antibodies to GH, and in the EU for the long-term treatment of growth failure in children and adolescents with severe primary IGF-I deficiency. Subcutaneous mecasermin 0.12 mg/kg twice daily stimulated linear growth in children with growth failure and severe IGF-I deficiency associated with GH insensitivity, according to the results of a noncomparative, multicenter trial (n = 76) [mean duration of therapy 4.4 years; range 0.04-12.5 years]. During the first year of treatment, height velocity significantly increased from a mean 2.8 cm/year at baseline to a mean 8.0 cm/year; mean growth velocities remained above baseline for up to 8 years. Mecasermin also promoted statural growth in a small noncomparative trial in children with growth failure and GH insensitivity syndrome (n = 8). After 6.5-7.5 years of mecasermin therapy, the mean increase in the height standard deviation score was +1.4. Mecasermin was also shown to have beneficial effects in various other conditions including diabetes mellitus and anorexia nervosa. Subcutaneous mecasermin was generally well tolerated in children with severe IGF-I deficiency associated with GH insensitivity.
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PMID:Mecasermin. 1848

Human Insulin-like growth factor 1 (hIGF-1) consists of 70 amino acids in a single chain with three intermolecular disulfide bridges possessing valuable therapeutic effects. To date, numerous variants of specifically engineered hIGF-1 have been produced so as to improve hIGF-1 biological activity, stability and stronger binding to IGF-1 receptor. Mecasermin is one of the modified variants with one amino acid substitution near the N-terminal (T4I) approved for the treatment of growth failure diabetes, wound healing, amyotrophic lateral sclerosis and severe primary IGF-1 deficiency. No scientific report for recombinant production of mecasermin in Escherichia coli (E. coli) expression system has been sofar reported. In the present study, we therefore investigated the overexpression of mecasermin in two different E. coli strains in order to obtain higher yield of recombinant protein. To achieve this goal, mecasermin DNA encoding sequence was designed based on polypeptide sequence, optimized according to E. coli codon preference, and cloned in pET15b. Recombinant vector, pET15-mecasermin, transferred into two E. coli strains rigami B (DE3) and BL21 (DE3) and induced for expression in a small scale. Results revealed the E. coli Origami B (DE3) expression system was a preferable host for mecasermin production due to its high expression level being around twice as much as BL21 (DE3). Large scale mecasermin production was performed in batch culture and produced recombinant protein specifically confirmed by western blotting and mass spectroscopy. Since major part of recombinant mecasermin was expressed as inclusion body, isolation and refolding was accomplished through developed purification procedure, and finally recombinant protein was successfully purified by gel filtration chromatography.
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PMID:Recombinant production of mecasermin in E. coli expression system. 2633 60