The human GLP-1 analogs liraglutide and semaglutide: absence of histopathological effects on the pancreas in nonhuman primates.

Increased pancreas mass and glucagon-positive adenomas have been suggested to be a risk associated with sitagliptin or exenatide therapy in humans. Novo Nordisk has conducted extensive toxicology studies, including data on pancreas weight and histology, in Cynomolgus monkeys dosed with two different human glucagon-like peptide-1 (GLP-1) receptor agonists. In a 52-week study with liraglutide, a dose-related increase in absolute pancreas weight was observed in female monkeys only.

Effect of ageing on the passive and active tension and pharmacodynamic characteristics of rat coronary arteries: age-dependent increase in sensitivity to 5-HT and K+.

The influence of ageing on the passive and active tension and pharmacodynamic characteristics of intramural coronary arteries from 3-month-old and 2-year-old male Wistar rats was investigated using an isometric myograph. The passive vessel wall tension measured in Ca(2+)-free physiological salt solution at L(0) was significantly greater in arteries from old rats (1.46 ± 0.

GLP-1 receptor agonists and the thyroid: C-cell effects in mice are mediated via the GLP-1 receptor and not associated with RET activation.

Liraglutide and exenatide are glucagon-like peptide receptor (GLP-1R) agonists used in the treatment of type 2 diabetes. Both molecules have been associated with the development of thyroid C-cell tumors after lifetime exposure in rodents. Previously, it has been reported that these tumors are preceded by increased plasma calcitonin and C-cell hyperplasia.

Age- and endothelium-dependent changes in coronary artery reactivity to serotonin and calcium.

The influence of ageing and endothelium removal on the sensitivity and contractile response of rat coronary arteries to intracellular Ca2+ ([Ca2+]i) during activation with serotonin (5-HT) and membrane depolarisation with 125 mM K+ was investigated. The sensitivity and contractile response of coronary arteries to 5-HT were significantly higher in 2-year-old than in 3-month-old rats. The receptor responsible for the 5-HT-induced contractions in coronary arteries belongs to a population of 5-HT2 receptors in both young and old rats based on the Schild plot.

Homologous desensitization of calcitonin gene-related peptide-induced relaxation in rat intramural coronary arteries.

We investigated the type of desensitization of calcitonin gene-related peptide (CGRP)-induced responses in rat isolated intramural coronary arteries using isometric myograph and FURA-2 technique. In coronary arteries precontracted with 9,11-dideoxy-11alpha,9alpha-epoxymethanoprostaglandin F2alpha (U46619), development of tachyphylaxis to CGRP is characterized by significant attenuation of CGRP-induced maximal reduction in the tension and [Ca2+](i) during the second CGRP concentration-response curve; however, there was no further reduction in the CGRP-induced maximum relaxation during the third CGRP concentration-response curve. There was no sign of tachyphylaxis to CGRP when CGRP concentration-response curves were recorded in 36 mM K+-depolarized coronary arteries contrary to the results obtained in 300 nM U46619-precontracted coronary arteries.