ABSTRACT
The combined glucose-lowering effect of exenatide and dapagliflozin has not yet been studied. We investigated this combination (single-dose or 4-week dosing) in diabetic ob/ob mice. Vehicle-corrected basal glucose showed greater reduction 1 h following exenatide + dapagliflozin than with exenatide or dapagliflozin alone, and stayed significantly lower for all groups versus vehicle over 3 h. During an oral glucose tolerance test, glucose excursion (30 min post-dose) was significantly lower for exenatide + dapagliflozin versus exenatide or dapagliflozin, or vehicle. Exenatide + dapagliflozin and exenatide, but not dapagliflozin alone, reduced glucose excretion over 24 h versus vehicle. After dosing for 4 weeks, exenatide, dapagliflozin and exenatide + dapagliflozin similarly decreased haemoglobin A1c (HbA1c). Body weight was reduced only with exenatide or exenatide + dapagliflozin. The glomerular filtration rate was similar with exenatide, dapagliflozin and vehicle, and increased with exenatide + dapagliflozin. Optimized combinatorial dosing of these antidiabetic agents may provide additive glucose lowering in type 2 diabetes mellitus.
Subject(s)
Diabetes Mellitus, Experimental/drug therapy , Glucosides/pharmacology , Hypoglycemic Agents/pharmacology , Peptides/pharmacology , Venoms/pharmacology , Animals , Benzhydryl Compounds , Biomarkers/blood , Blood Glucose/drug effects , Blood Glucose/metabolism , Body Weight , Diabetes Mellitus, Experimental/blood , Exenatide , Glycated Hemoglobin/drug effects , Glycated Hemoglobin/metabolism , Male , Mice , Mice, Inbred NODABSTRACT
AIM: Our objective was to document the clinical and pathological findings in eight patients with gastric carcinoids seen in our institution over a 16-year period (1980-96). METHODS: All cases reported during this period as microcarcinoids, atypical carcinoids and mixed carcinoid-carcinoma of the stomach were retrieved from pathology records. Eight cases with typical histologic features of carcinoid were studied. RESULTS: Seven cases were men (median age 53 years, range 35-55). Four patients presented with upper abdominal pain. Serum gastrin level was elevated in two cases. The endoscopic appearances and the endoscopic biopsy histology were not diagnostic. Surgical treatment ranged from simple nodule excision to partial, subtotal or extended gastrectomy and Whipple's pancreatico-duodenectomy. Lymph node and liver metastasis were seen in four patients each. The median duration of follow-up was one year. CONCLUSION: Gastric carcinoids have varied etiopathogenesis. These may arise in a background of hypergastrinemic conditions or may be sporadic. Most appear to be slow growing but aggressive neoplasms are capable of distant metastasis.
