Performance and risks of ChatGPT used in drug information: an exploratory real-world analysis.

OBJECTIVES: To investigate the performance and risk associated with the usage of Chat Generative Pre-trained Transformer (ChatGPT) to answer drug-related questions. METHODS: A sample of 50 drug-related questions were consecutively collected and entered in the artificial intelligence software application ChatGPT. Answers were documented and rated in a standardised consensus process by six senior hospital pharmacists in the domains content (correct, incomplete, false), patient management (possible, insufficient, not possible) and risk (no risk, low risk, high risk). As reference, answers were researched in adherence to the German guideline of drug information and stratified in four categories according to the sources used. In addition, the reproducibility of ChatGPT's answers was analysed by entering three questions at different timepoints repeatedly (day 1, day 2, week 2, week 3). RESULTS: Overall, only 13 of 50 answers provided correct content and had enough information to initiate management with no risk of patient harm. The majority of answers were either false (38%, n=19) or had partly correct content (36%, n=18) and no references were provided. A high risk of patient harm was likely in 26% (n=13) of the cases and risk was judged low for 28% (n=14) of the cases. In all high-risk cases, actions could have been initiated based on the provided information. The answers of ChatGPT varied over time when entered repeatedly and only three out of 12 answers were identical, showing no reproducibility to low reproducibility. CONCLUSION: In a real-world sample of 50 drug-related questions, ChatGPT answered the majority of questions wrong or partly wrong. The use of artificial intelligence applications in drug information is not possible as long as barriers like wrong content, missing references and reproducibility remain.

The significance of the nuclear farnesoid X receptor (FXR) in ß cell function.

Bile acids (BAs) are important signaling molecules that are involved in the regulation of their own metabolism, lipid metabolism, energy expenditure and glucose homeostasis. The nuclear farnesoid X receptor (FXR) and the G-protein-coupled TGR-5 are the most prominent BA receptors. FXR is highly expressed in liver and activation of liver FXR profoundly affects glucose homeostasis. Strikingly, the effect of FXR activation on glucose metabolism seems to depend on the nutritional status of the organism, i.e., slimness or obesity. Recently, it became evident that FXR is present in pancreatic ß cells and that activation of ß cell FXR contributes to the regulation of glucose homeostasis. Interestingly, FXR activation increases glucose-induced insulin secretion by non-genomic effects on stimulus-secretion coupling. The first chapter of this review shortly introduces the role of liver FXR in glucose metabolism, the second part focuses on the impact of FXR in lean and obese animals, and the third chapter highlights the significance of FXR in ß cells.

Bile acids acutely stimulate insulin secretion of mouse ß-cells via farnesoid X receptor activation and K(ATP) channel inhibition.

Type 2 diabetes mellitus is associated with alterations in bile acid (BA) signaling. The aim of our study was to test whether pancreatic ß-cells contribute to BA-dependent regulation of glucose homeostasis. Experiments were performed with islets from wild-type, farnesoid X receptor (FXR) knockout (KO), and ß-cell ATP-dependent K(+) (K(ATP)) channel gene SUR1 (ABCC8) KO mice, respectively. Sodium taurochenodeoxycholate (TCDC) increased glucose-induced insulin secretion. This effect was mimicked by the FXR agonist GW4064 and suppressed by the FXR antagonist guggulsterone. TCDC and GW4064 stimulated the electrical activity of ß-cells and enhanced cytosolic Ca(2+) concentration ([Ca(2+)](c)). These effects were blunted by guggulsterone. Sodium ursodeoxycholate, which has a much lower affinity to FXR than TCDC, had no effect on [Ca(2+)](c) and insulin secretion. FXR activation by TCDC is suggested to inhibit K(ATP) current. The decline in K(ATP) channel activity by TCDC was only observed in ß-cells with intact metabolism and was reversed by guggulsterone. TCDC did not alter insulin secretion in islets of SUR1-KO or FXR-KO mice. TCDC did not change islet cell apoptosis. This is the first study showing an acute action of BA on ß-cell function. The effect is mediated by FXR by nongenomic elements, suggesting a novel link between FXR activation and K(ATP) channel inhibition.