Sequence of human insulin gene
ABSTRACT The human insulin gene contains two intervening sequences, one is within the region transcribed into the 5'-untranslated segment of the mRNA and the other interrupts the C-peptide encoding region. A comparison of the human with the rat insulin genes indicates potential regulatory regions in the DNA segment preceding the gene and suggests that the ancestral form of the insulin gene had two intervening sequences.
Full-textDOI: · Available from: Howard M Goodman, Jun 26, 2014
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- "The signal peptide (the first 23–24 aa at the N-terminus) is removed during insertion into the endoplasmic reticulum, resulting in proinsulin (86 aa, ~9.5 kDa). Proinsulin consists of three domains: an amino-terminal B chain (30 aa, ~3.4 kDa), a carboxy-terminal A chain (21 aa, ~2.4 kDa) and a connecting C chain (34 aa, ~3.0 kDa)78. Within the endoplasmic reticulum, proinsulin is cut by neuroendocrine-cell-specific prohormone convertases (PC1 and PC2) to excise the C chain. "
ABSTRACT: There is a steady increasing demand for insulin worldwide. Current insulin manufacturing capacities can barely meet this increasing demand. The purpose of this study was to test the feasibility of producing human proinsulin in the milk of transgenic animals. Four lines of transgenic mice harboring a human insulin cDNA with expression driven by the goat β-casein gene promoter were generated. The expression level of human proinsulin in milk was as high as 8.1 g/L. The expression of the transgene was only detected in the mammary gland during lactation, with higher levels at mid-lactation and lower levels at early and late lactation. The blood glucose and insulin levels and the major milk compositions were unchanged, and the transgenic animals had no apparent health defects. The mature insulin derived from the milk proinsulin retained its biological activity. In conclusion, our study provides supporting evidence to explore the production of high levels of human proinsulin in the milk of dairy animals.Scientific Reports 09/2014; 4:6465. DOI:10.1038/srep06465 · 5.58 Impact Factor
- "This has been best achieved by basal-bolus therapy using multiple daily injections or continuous subcutaneous insulin infusion pumps. There have been many major breakthroughs since 1922, but none more important than the cloning and sequencing of the insulin gene in 1980,2 which brought about the introduction of unlimited supplies of bacterially expressed human insulin and the technology to modify the structure of the protein, such that there are now at least six rapid-acting or long-acting analogues. Combined with advances in glucose monitoring, these modified insulins have allowed patients to control their blood glucose levels within relatively narrow limits. "
Article: Cell Therapy for Type 1 Diabetes[Show abstract] [Hide abstract]
ABSTRACT: Cell therapy in the form of human islet transplantation has been a successful form of treatment for patients with type 1 diabetes for over 10 years, but is significantly limited by lack of suitable donor material. A replenishable supply of insulin-producing cells has the potential to address this problem; however to date success has been limited to a few preclinical studies.Two of the most promising strategies include differentiation of embryonic stem cells and induced pluripotent stem cells towards insulin producing cells and transdifferentiation of acinar or other closely related cell types towards β-cells. Here we discuss recent progress and challenges that need to be overcome in taking cell therapy to the clinic.QJM: monthly journal of the Association of Physicians 01/2014; 107(4). DOI:10.1093/qjmed/hcu025 · 2.50 Impact Factor
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- "The human insulin superfamily consists of ten members including a single insulin (Bell et al. 1980), IGF1 and IGF2 (Rinderknecht and Humbel 1978), relaxins (Bedarkar et al. 1977), relaxin-like growth factors (Bullesbach and Schwabe 1995) and an early placental insulin-like peptide (Chassin et al. 1995). We focus our discussion of neural modulation and behavior on the role of three genes: insulin, IGF1 and IGF2 (Bell et al. 1980; Harper et al. 1981; Owerbach et al. 1980). Similar to the rat and mouse insulin genes, the mammalian insulin gene encodes a preproinsulin peptide, which has an A-chain, B-chain, C-peptide and signal sequence (Murray-Rust et al. 1992). "
ABSTRACT: Insulin signaling plays a critical role in coupling external changes to animal physiology and behavior. Despite remarkable conservation in the insulin signaling pathway components across species, divergence in the mechanism and function of the signal is evident. Focusing on recent findings from C. elegans, D. melanogaster and mammals, we discuss the role of insulin signaling in regulating adult neuronal function and behavior. In particular, we describe the transcription-dependent and transcription-independent aspects of insulin signaling across these three species. Interestingly, we find evidence of diverse mechanisms underlying complex networks of peptide action in modulating nervous system function.Invertebrate Neuroscience 01/2014; 14(2). DOI:10.1007/s10158-013-0166-9 · 0.90 Impact Factor