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Type 2 diabetes (T2D), the major type of diabetes mellitus (DM), is a long term metabolic disorder primarily occurs as a result of obesity and not enough exercise.  T2D is characterized by high blood sugar, insulin resistance, and relative lack of insulin. It is reported that T2D could lead to a ten-year-shorter life expectancy. Globally, near to 400 million people are suffering from T2D and the rate is still rising. 
2. Introduction-Insulin, GLP1, GLP1R
Insulin is a peptide hormone which plays a crytical role in the progresses of T2D disease.  The human insulin gene primarily encodes preproinsulin which is a peptide containing 110 amino acids. Preproinsulin is further processed into proinsulin by removal of the N-terminal signal peptide. Afeter that, three peptides (B chain, A chain and C-peptide) are released by post-translational modification. The human insulin protein is a dimer of the A-chain and B-chain linked by disulfide bonds.
Glucagon-like peptide-1 (GLP-1) is a peptide hormone and an incretin derived from preproglucagon protein which in human is encoded by the GCG gene. GLP-1 can increase insulin secretion and decrease glucagon secretion from the pancreas in a glucose-dependent manner. The human glucagon-like peptide 1 receptor (GLP1R) is G protein-coupled receptor encoded by the GLP1R gene. GLP1R binds GLP-1 and glucagon as its natural endogenous agonists.
The GLP1R system has become an important target for T2D treatment.
3. T2D Therapies-DPP4 Inhibitors, GLP1R Agonists
There are mainly two classes of glucose-lowering therapeutics: dipeptidyl peptidase 4 (DPP-4) inhibitors and GLP1R agonists. Both GLP1R agonists and DPP-4 inhibitors affect glucose control via multiple mechanisms, including increase of glucose-dependent insulin secretion, slowed gastric emptying, and reduction of postprandial glucagon and of food intake. These agents have a lower risk of causing hypoglycemia.
3.1) DPP-4 enzyme inhibitors
DPP-4 protein, also known as adenosine deaminase complexing protein 2 or CD26, is encoded by human DPP4 gene. DPP-4 plays a key role in glucose metabolism.  It is associated with the rapid degradation of incretins including GLP-1, which renders GLP-1 a short half-life, namely less than two minutes.
To circumvent the half-life constraint of GLP-1, multiple DPP-4 inhibitors have been developed, such as Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin, Gemigliptin, Anagliptin, Teneligliptin, Alogliptin, Trelagliptin, Omarigliptin (MK-3102), Evogliptin, Dutogliptin etc. These DPP-4 inhibitors prolong and enhance the activity of incretins including GLP-1 through inhibiting the DPP-4 enzyme, which in turn increases glucose-dependent insulin secretion and suppresses inappropriately elevated glucagon secretion.
3.2) GLP1R agonists
GLP-1R agonists mimic the activities of GLP-1. These agents exhibit increased resistance to DPP-4 degradation by virtue of their amino acid sequence and/or through chemical modification, and thus provide pharmacological levels of GLP-1.
There are several approved GLP-1 agonists, such as exenatide, liraglutide, lixisenatide, albiglutide and dulaglutide etc., with more being developed. These agents work in the same pathway as DPP-4 inhibitors but are generally considered more potent.
Stable cells expressing the GLP-1 receptor are a powerful and indispensable tool during the process of screening novel GLP1R agonists.
4. Our Capabilities
We can offer several agents related to research of GLP1-based T2D treatment, including but not limited to the following products. Please contact us for special requirements, we are always happay to provide custom services to assist your research.
|cDNA||Human INS ORF clone|
|Human GCG ORF clone|
|Human DPP4 cDNA clone|
|Human GLP1R ORF Clone|
|shRNA||shRNA set against human INS|
|shRNA set against human GCG|
|shRNA set against human DPP4|
|shRNA set against Human GLP1R|
|3’UTR||Human INS miRNA 3'UTR clone|
|Human GCG miRNA 3'UTR clone|
|Human DPP4 miRNA 3'UTR clone|
|Human GLP1R miRNA 3'UTR clone|
|Virus particles||Human INS lentiviral particles|
|Human GCG lentivirus particles|
|Human GCG adenoviral particles|
|Human DPP4 lentivirus particles|
|Human DPP4 adenoviral particles|
|Human GLP1R lentivirus particles|
|Human GLP1R adenoviral particles|
|Stable cell lines||Human INS stable cell line|
|Human GCG stable cell line|
|Human DPP4 stable cell line|
|Human GLP1R stable cell lines|