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Acute Exenatide Therapy Attenuates Postprandial Vasodilation in Humans with Prediabetes: A Randomized Controlled Trial.
Hamidi, V, Riggs, K, Zhu, L, Bermudez Saint Andre, K, Westby, C, Coverdale, S, Dursteler, A, Wang, H, Miller Iii, C, Taegtmeyer, H, et al
Metabolic syndrome and related disorders. 2020;(5):225-233
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Abstract
Background: The state of prediabetes comprises atherosclerotic changes leading to decreased vascular function in humans. This study examined the effects on incretin mimetics on vascular physiology in the prediabetic postprandial state. Methods: Fifteen obese adults with prediabetes participated in a randomized, crossover, double-blinded trial comparing the postprandial effects of exenatide, saxagliptin, and placebo on peripheral vasodilation. All studies utilized a standardized high-fat meal. Resting and peak forearm blood flow (FBF) were measured via strain gauge venous occlusion plethysmography, and makers of vascular dysfunction were measured in plasma. Results: Exenatide attenuated resting FBF at 3 hr (P = 0.003) and 6 hr (P = 0.056) postmeal, compared to placebo. Nonsignificant reductions in resting FBF were observed between saxagliptin and placebo at the same time points. No group differences were observed for peak FBF, plasma nitrotyrosine, and plasma 8-iso-prostaglandin F2alpha. A transient increase in plasma triglyceride was abated in the exenatide group, when compared to saxagliptin and placebo groups. Only exenatide group showed no significant upsurge in plasma insulin. Plasma-free fatty acids significantly declined in all three groups, although less markedly for exenatide. Postmeal glucose increased at 2 hr with placebo and saxagliptin, but simultaneously decreased with exenatide. Conclusions: Acute treatment with exenatide blunted the postprandial vasodilatory effect of a high-fat meal in prediabetes. Exenatide's acute effects derived primarily from multiple endothelium-independent processes. Trial Registration Number: NCT02104739.
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Emerging role of GIP and related gut hormones in fertility and PCOS.
Moffett, RC, Naughton, V
Peptides. 2020;:170233
Abstract
Gastric inhibitory polypeptide (GIP) is best known as an incretin hormone released by enteroendocrine K-cells in response to feeding and stimulates insulin release to regulate blood glucose and nutrient homeostasis. More recently GIP has been ascribed a positive role in lipid metabolism, bone strength, cardiovascular function and cognition. The present paper considers an emerging role of GIP and related gut hormones in fertility and especially polycystic ovarian syndrome (PCOS). Key evidence concerns restoration of fertility in women with gross obesity and PCOS following bariatric surgery. This is considered to reflect indirect effects mediated by alleviation of insulin resistance together with possible direct effects of surgically induced changes of GIP, GLP-1 and related peptide hormones on ovaries and the hypothalamic-pituitary-adrenal axis. Further studies are required to determine inter-relationships between the hormones and cellular mechanisms involved but these observations suggest that GIP and other gut may provide a novel therapeutic approach for PCOS and other reproductive disorders.