Glucagon ELISA Kit

Postprandial glucose excursions are postulated to increase the risk for diabetes complications via the production of advanced glycation end products (AGEs). The soluble receptor of AGEs (sRAGE) likely acts as a decoy receptor, mopping up AGEs, diminishing their capacity for pro-inflammatory and pro-apoptotic signaling. Recent evidence suggests that AGEs and soluble receptor for AGEs (sRAGE) may be altered under postprandial and fasting conditions. Here, we investigated the effects of increasing oral glucose loads during oral glucose tolerance tests (OGTT) and matched isoglycaemic intravenous (i.v.) glucose infusions (IIGI) on circulating concentrations of sRAGE. Samples from eight individuals with type 2 diabetes and eight age-, gender-, and body mass index (BMI)-matched controls, all of whom underwent three differently dosed OGTTs (25 g, 75 g, and 125 g), and three matched IIGIs were utilised (NCT00529048). Serum concentrations of sRAGE were measured over 240 min during each test. For individuals with diabetes, sRAGE area under the curve (AUC(0-240) (min)) declined with increasing i.v. glucose dosages (p < 0.0001 for trend) and was lower during IIGI compared to OGTT at the 125 g dosage (p = 0.004). In control subjects, sRAGE AUC(0-240) (min) was only lower during IIGI compared to OGTT at the 25 g dose (p = 0.0015). sRAGE AUC(0-240) (min) was negatively correlated to AUC(0-240) (min) for the incretin hormone glucagon-like peptide -1 (GLP-1) during the 75 g OGTT and matched IIGI, but only in individuals with type 2 diabetes. These data suggest that gastrointestinal factors may play a role in regulating sRAGE concentrations during postprandial glucose excursions, thus warranting further investigation.

Background: Glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide receptor (GIPR) co-agonists have emerged as treatment options for reversing diabetes and obesity. Here, we screened the high potency receptor-biased GLP-1R agonists via a newly designed high-throughput GLP-1R extracellular domain (ECD)-based system and demonstrated its in vitro and in vivo therapeutic characters. Methods: Twelve 9-mer peptides (named XEL1-XEL12) which were screened from a large phage-displayed peptide library were fused to the N-terminus of GIP (3-30) to generate another twelve fusion peptides, termed XEL13-24. Using the six lysine-altered XEL17 as leading sequences, eighteen fatty chain modified fusion peptides were further assessed via in vitro GLP-1R/GIPR-based cell assay. Moreover, the acute and long-acting in vivo effects of selected candidate on diabetic db/db mice and diet-induced obesity (DIO) rats were both carefully evaluated. Results: XEL17 exhibited balanced activation potency on GLP-1R/GIPR in stable cell lines, and further assessment was performed to evaluate the XEL32, a fatty chain modified XEL17 derivative. Preclinical pharmacodynamic results in diabetic db/db mice demonstrated that XEL32 held outstanding insulinotropic and glucose lowering activities. In addition, protracted antidiabetic effects of XEL32 were also proved by the hypoglycemic test and multiple oral glucose tolerance test. Furthermore, chronic treatment of XEL32 in DIO rats exhibited outstanding beneficial effects on body weight control, fat loss, food intake control, hemoglobin A1C (HbA1C) reduction as well as the glucose tolerance. Conclusions: XEL32, as a novel GLP-1/GIP dual receptor agonist, may supply efficient glycemic control and weight loss.