Mouse Anti-Human GLP-1(aa 1-36) monoclonal antibody, clone N92690

The free fatty acid receptor G protein-coupled receptor 120 (GPR120) is expressed in pancreatic islets, but its specific cell distribution and function have not been fully established. In this study, a GPR120-IRES-EGFP knockin (KI) mouse was generated to identify GPR120-expressing cells with enhanced green fluorescence proteins (EGFP). EGFP-positive cells collected from KI mouse islets by flow cytometry had a significantly higher expression of pancreatic polypeptide (PP) evidenced by reverse transcriptase (RT)-quantitative polymerase chain reaction (qPCR). Single-cell RT-PCR and immunocytochemical double staining also demonstrated the coexpression of GPR120 with PP in mouse islets. The GPR120-specific agonist TUG-891 significantly increased plasma PP levels in mice. TUG-891 significantly increased PP levels in islet medium in vitro, which was markedly attenuated by GPR120 small interfering RNA treatment. TUG-891-stimulated PP secretion in islets was fully blocked by pretreatment with YM-254890 (a Gq protein inhibitor), U73122 (a phospholipase C inhibitor), or thapsigargin (an inducer of endoplasmic reticulum Ca2+ depletion), respectively. TUG-891 triggered the increase in intracellular free Ca2+ concentrations ([Ca2+]i) in PP cells, which was also eliminated by YM-254890, U73122, or thapsigargin. GPR120 gene expression was significantly reduced in islets of high-fat diet (HFD)-induced obese mice. TUG-891-stimulated PP secretion was also significantly diminished in vivo and in vitro in HFD-induced obese mice compared with that in normal-chow diet control mice. In summary, this study demonstrated that GPR120 is expressed in mouse islet PP cells and GPR120 activation stimulated PP secretion via the Gq/PLC-Ca2+ signaling pathway in normal-chow diet mice but with diminished effects in HFD-induced obese mice.

Background: The global incidence of type 2 diabetes (T2D) continues to increase annually, and persons with T2D typically require regular changes in pharmacologic invention for achieving glycemic targets. Healthcare providers must consider multiple factors when selecting a 2nd line. This retrospective cohort study evaluates impact of two common anti-diabetes medication classes (dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists) on the well-known composite 3-point major cardiovascular events outcome (3P-MACE, comprised of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke). No significant impact was found. Persons with T2D face increased risks of many adverse cardiovascular outcomes. This study duplicated common inclusion and exclusion criteria to create an observational cohort from a large healthcare system's electronic health records for testing DPP-4i and GLP-1RA against each other to evaluate impact on likelihood to develop 3P-MACE. Methods: The statistical model and analyses were based on a cohort of 5,518 adult patients with T2D who were prescribed metformin and either DPP-4i or GLP-1RA to control glycemia during clinic visits between January 2005 and September 2019. A Cox proportional hazards model was developed from the cohort to predict the 3P-MACE endpoint. Results: The model did not show a meaningful difference in likelihood of developing the 3P-MACE outcome between patients treated with DPP-4i compared to patients treated with GLP-1RA. Conclusions: Prior history of cardiovascular disease (CVD) did not impact this small difference between the two classes of drug.