Part:BBa_K3096030
Exendin-4 (GLP-1 analogue) with secretion signal
Exendin-4 is an analogue of H. suspectum to human GLP-1. Here with secretion signal (KR 1020120130606-A/1: Secretion signal peptide linked Exendin-4 gene transduced pancreatic islet cluster for treatment of type I diabetes).
Background
In the iGEM Team Tübingen 2019 project, Exendin-4 was used as a therapeutic for the treatment of Type 2 Diabetes mellitus with probiotics. Exendin-4 is, in contrast to its human analogue more stable and not as easily degraded by DPP-IV peptidase. Thus, a suitable candidate for a therapeutic.
Usage and Biology
Exendin-4 is used as a treatment for Type 2 Diabetes mellitus. The glucagon like peptide binds to a GPCR on the pancreatic beta cells, which will cause an intracellular cascade activating an Adenylate Cyclase. If ATP is available within the cell, which means if the cell has already taken up sugar and run through glycolysis, cAMP will be produced (Jens Juul Holst, 2007). Overall, this will result in prolonged depolarization and calcium ion influx and consequently more secretion of insulin from the beta cells (Jens Juul Holst, 2007). This increase in insulin secretion can overcome the relative lack of insulin in the periphery of Type 2 Diabetes mellitus(Jens Juul Holst, 2007). Exendin-4 does not only have a direct effect on the pancreas, but also decreases gastrointestinal motility and secretion, hunger and the emptying of the stomach, thus helping in weight reduction (Jens Juul Holst, 2007). Additionally, it is considered to be cardioprotective(Jens Juul Holst, 2007). This is very important for the therapy, since many cases of Type 2 DM are caused by an unhealthy lifestyle and obesity(Jens Juul Holst, 2007).
Sequence and Features
- 10COMPATIBLE WITH RFC[10]
- 12COMPATIBLE WITH RFC[12]
- 21COMPATIBLE WITH RFC[21]
- 23COMPATIBLE WITH RFC[23]
- 25COMPATIBLE WITH RFC[25]
- 1000COMPATIBLE WITH RFC[1000]
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