exenatide and Hypercholesterolemia

Beyond glycemic control, applications of glucagon-like peptide-1 receptor (GLP-1r) agonists (GLP-1 RAs) inhibit inflammation and plaque development in murine atherosclerotic models. However, whether they modulate hematopoietic stem/progenitor cells (HSPCs) to prohibit skewed myelopoiesis in hypercholesteremia remains unknown. In this study, GLP-1r expression in fluorescence-activated cell sorting (FACS)-sorted wild-type HSPCs was determined by capillary western blotting. Bone marrow cells (BMCs) of wild-type or GLP-1r-/- mice were transplanted into lethally irradiated low-density lipoprotein receptor deficient (LDLr-/-) recipients followed by high-fat diet (HFD) for chimerism analysis by FACS. In parallel, LDLr-/- mice were placed on HFD for 6 weeks and then treated with saline or Exendin-4 (Ex-4) for another 6 weeks. HSPC frequency and cell cycle were analyzed by FACS, and intracellular metabolite levels were assessed by targeted metabolomics. The results demonstrated that HSPCs expressed GLP-1r and transplantation of GLP-1r-/- BMCs resulted in skewed myelopoiesis in hypercholesterolemic LDLr-/- recipients. In vitro, Ex-4 treatment of FACS-purified HSPCs suppressed cell expansion and granulocyte production induced by LDL. In vivo, Ex-4 treatment inhibited plaque progression, suppressed HSPC proliferation, and modified glycolytic and lipid metabolism in HSPCs of hypercholesteremic LDLr-/- mice. In conclusion, Ex-4 could directly inhibit HSPC proliferation induced by hypercholesteremia.

Topics: Animals; Atherosclerosis; Cell Proliferation; Exenatide; Hematopoietic Stem Cell Transplantation; Hypercholesterolemia; Mice; Mice, Inbred C57BL

Cardiovascular effects of glucagon-like peptide-1 receptor (GLP-1R) agonist therapies are potentially mediated by anti-inflammatory effects on atherosclerosis. Our study demonstrates that

Topics: Acetates; Animals; Apolipoproteins B; Atherosclerosis; Diabetes Mellitus, Experimental; Exenatide; Female; Gallium Radioisotopes; Glucagon-Like Peptide-1 Receptor; Heterocyclic Compounds, 1-Ring; Hypercholesterolemia; Insulin-Like Growth Factor II; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Positron-Emission Tomography; Receptors, LDL

To determine whether exenatide is effective in reducing weight and glycosylated hemoglobin level (HbA1c), and to investigate its efficacy in improving lipid profile, blood pressure, and creatinine levels in the Arab population.. This study was conducted at the Endocrine Unit, Dubai Hospital, Dubai, United Arab Emirates. We retrospectively collected data from patients with type 2 diabetes started on exenatide between November 2011 and February 2012. Data included demographics, clinical, laboratory results, and medications used. A general linear model adjusted by baseline characteristics (weight, HbA1C, age, use of statins, and duration of diabetes) was used to assess changes between baseline and end of trial in HbA1C, weight, low density lipoprotein cholesterol, total cholesterol, triglycerides, creatinine, and blood pressure.. After 6 months of treatment with exenatide, the HbA1c decreased by 0.47% (95% confidence level [CI]: -0.01 - 0.95) (p=0.055). Weight reduction was highly significant; 5.6 kg (95% CI: 3.34 - 7.85) (p<0.001). Those reductions remained significant after adjustment for confounding factors.. This study showed that weight reduction was highly significant with exenatide. The borderline significance in HbA1c reduction can be attributed to the small sample size. 

Topics: Adult; Arabs; Blood Pressure; Cholesterol, LDL; Diabetes Mellitus, Type 2; Exenatide; Female; Glycated Hemoglobin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypoglycemic Agents; Male; Middle Aged; Obesity; Peptides; Retrospective Studies; Triglycerides; United Arab Emirates; Venoms; Weight Loss