High insulin levels do not influence PC‐1 gene expression and protein content in human muscle tissue and hepatoma cells

Frittitta, Lucia; Sbraccia, Paolo; Costanzo, Benedetta V.; Tassi, Vittorio; D’Adamo, Monica; Spampinato, Daniela; Ercolino, Tonino; Purrello, Francesco; Tamburrano, G.; Vigneri, Riccardo; Trischitta, Vincenzo

doi:10.1002/(sici)1520-7560(200001/02)16:1<26::aid-dmrr78>3.3.co;2-e

Cited by 4 publications

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“…Mammalian cell‐based assays were performed to test the ability of plant‐derived DesB 30 ‐insulin to trigger insulin signal transduction through autophosphorylation of IRβ (White, 1998). HepG2 cells [human hepatocellular carcinoma epithelial cells, ATCC HB‐8065; American Type Culture Collection (ATCC), Manassas, VA, USA] express insulin receptors and have been used previously to demonstrate insulin signalling (Frittitta et al ., 2000; Senn et al ., 2003).…”

Section: Methodsmentioning

confidence: 99%

Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds

Nykiforuk

Boothe

Murray

et al. 2005

Plant Biotechnology Journal

141

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SummaryThe increased incidence of diabetes, coupled with the introduction of alternative delivery methods that rely on higher doses, is expected to result in a substantial escalation in the demand for affordable insulin in the future. Limitations in the capacity and economics of production will make it difficult for current manufacturing technologies to meet this demand. We have developed a novel expression and recovery technology for the economical manufacture of biopharmaceuticals from oilseeds. Using this technology, recombinant human precursor insulin was expressed in transgenic plants. Plant-derived insulin accumulates to significant levels in transgenic seed (0.13% total seed protein) and can be enzymatically treated in vitro to generate a product with a mass identical to that of the predicted product, DesB 30 -insulin. The biological activity of this product in vivo and in vitro was demonstrated using an insulin tolerance test in mice and phosphorylation assay performed in a mammalian cell culture system, respectively.

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Section: Methodsmentioning

confidence: 99%

Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds

Nykiforuk

Boothe

Murray

et al. 2005

Plant Biotechnology Journal

141

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“…In several instances, the 3 UTRs may regulate gene expression through the modulation of mRNA stability (Day and Tuite 1998;Xia et al 1998;Frittitta et al 2001). Accordingly, PTP1B mRNA levels were measured in skeletal-muscle specimens by competitive PCR, as described elsewhere (Frittitta et al 2000).…”

Section: Figurementioning

confidence: 99%

A Variation in 3′ UTR of hPTP1B Increases Specific Gene Expression and Associates with Insulin Resistance

Paola¹,

Frittitta

Miscio³

et al. 2002

The American Journal of Human Genetics

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175

122

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Protein tyrosine phosphatase 1B (PTP1B) inhibits insulin signaling and, when overexpressed, plays a role in insulin resistance (Ahmad et al. 1997). We identified, in the 3' untranslated region of the PTP1B gene, a 1484insG variation that, in two different populations, is associated with several features of insulin resistance: among male individuals, higher values of the insulin resistance HOMA(IR) index (P=.006), serum triglycerides (P=.0002), and total/HDL cholesterol ratio (P=.025) and, among female individuals, higher blood pressure (P=.01). Similar data were also obtained in a family-based association study by use of sib pairs discordant for genotype (Gu et al. 2000). Subjects carrying the 1484insG variant showed also PTP1B mRNA overexpression in skeletal muscle (6,166 plus minus 1,879 copies/40 ng RNA vs. 2,983 plus minus 1,620; P<.01). Finally, PTP1B mRNA stability was significantly higher (P<.01) in human embryo kidney 293 cells transfected with 1484insG PTP1B, as compared with those transfected with wild-type PTP1B. Our data indicate that the 1484insG allele causes PTP1B overexpression and plays a role in insulin resistance. Therefore, individuals carrying the 1484insG variant might particularly benefit from PTP1B inhibitors, a promising new tool for treatment of insulin resistance (Kennedy and Ramachandran 2000).

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“…PC-1 gene expression. RNA extraction, reverse transcription, and competitive PCR were performed as previously described (11). Functional studies on mRNA stability Mutagenesis.…”

Section: Subjects a Total Of 205 Nonobese (Bmi ͻ30 Kg/mmentioning

confidence: 99%

A Cluster of Three Single Nucleotide Polymorphisms in the 3′-Untranslated Region of Human Glycoprotein PC-1 Gene Stabilizes PC-1 mRNA and Is Associated With Increased PC-1 Protein Content and Insulin Resistance–Related Abnormalities

et al. 2001

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Glycoprotein PC-1 inhibits insulin signaling and, when overexpressed, plays a role in human insulin resistance. Mechanisms of PC-1 overexpression are unknown. We have identified a haplotype in the 3-untranslated region of the PC-1 gene that may modulate PC-1 expression and confer an increased risk for insulin resistance. Individuals from Sicily, Italy, carrying the "P" haplotype (i.e., a cluster of three single nucleotide polymorphisms: G2897A, G2906C, and C2948T) were at higher risk (P < 0.01) for insulin resistance and had higher (P < 0.05) levels of plasma glucose and insulin during an oral glucose tolerance test and higher levels of cholesterol, HDL cholesterol, and systolic blood pressure. They also had higher (P < 0.05-0.01) PC-1 protein content in both skeletal muscle and cultured skin fibroblasts. In CHO cells transfected with either P or wild-type cDNA, specific PC-1 mRNA half-life was increased for those transfected with P (t/2 ‫؍‬ 3.73 ؎ 1.0 vs. 1.57 ؎ 0.2 h; P < 0.01). In a population of different ethnicity (Gargano, East Coast Italy), patients with type 2 diabetes (the most likely clinical outcome of insulin resistance) had a higher P haplotype frequency than healthy control subjects (7.8 vs. 1.5%, P < 0.01), thus replicating the association between the P allele and the insulin resistance-related abnormalities observed among Sicilians. In conclusion, we have identified a possible molecular mechanism for PC-1 overexpression that confers an increased risk for insulin resistance-related abnormalities.

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High insulin levels do not influence PC‐1 gene expression and protein content in human muscle tissue and hepatoma cells

Cited by 4 publications

References 0 publications

Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds

Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds

A Variation in 3′ UTR of hPTP1B Increases Specific Gene Expression and Associates with Insulin Resistance

A Cluster of Three Single Nucleotide Polymorphisms in the 3′-Untranslated Region of Human Glycoprotein PC-1 Gene Stabilizes PC-1 mRNA and Is Associated With Increased PC-1 Protein Content and Insulin Resistance–Related Abnormalities

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