Nicotinic acid timed to feeding reverses tissue lipid accumulation and improves glucose control in obese Zucker rats[S]

Involvement of the metabolic sensor GPR81 in cardiovascular control

“…These results are consistent with our hypothesis that suppression of lipolysis, especially in the postprandial state, would enhance glucose control due to decreased FFA fuel competition with glucose and increased insulin sensitivity (56,57). Therefore, achieving postprandial substance exposure was an important consideration in the design of the repeated-dosing studies.…”

“…The current lack of body weight gain with GPR81 agonism is probably due to incomplete around-the-clock FFA suppression. This result is analogous to other principles that partially inhibit lipolysis, e.g., following partial deactivation of hormone-sensitive lipase (58) or intermittent GPR109a activation (57,59). While the metabolic effects are impressive, these unfortunately occur at agonist exposures causing hypertension.…”

Dose-Response-Time Data Analysis: An Underexploited Trinity

“…The standard pharmacological approach of activating a target around the clock often fails because of time-dependent loss of drug efficacy and postdosing rebound above predose baseline levels. This case study presents data that originally explored the idea that a more comprehensive understanding of the relationship between plasma exposure and a pharmacological response combined with knowledge of the physiologic regulation of metabolism (i.e., simultaneously analyzed considering the effect of key biomarkers) can be used to mitigate these barriers, allowing the invention of new pharmacostrategies (Andersson et al, 2017;Kroon et al, 2017). The metaanalysis aimed at investigating in what way our inference about the system is changed when all drug exposure data are removed.…”

“…Data on cortisol-adrenocorticotropic hormone (ACTH) dynamics (Urquhart and Li, 1968), locomotor activity (van Rossum and van Koppen, 1968), and Brief Psychiatric Rating Scale (BPRS) scores (Lewander et al, 1990) were scanned from the literature. Case study 8 is a summary of Kroon et al (2017). Some of the figures and datasets have been used for teaching and at various conferences.…”

Comparative Chemomapping of Phytoconstituents from Different Extracts of Globe Artichoke - Cynara Scolymus L.

“…It has been demonstrated that the nicotinic acid can inhibit lipolysis, acutely reducing plasma free fatty acid concentrations, and my act in much the same manner as cynarin [58]. We are describing for the first time the incidence of pantothenic acid, pyridoxal and pyridoxine in artichoke extracts, while the above mentioned B5 and B6 vitamins were suggested to act as cancer risk reduction agents [59], and having anti-inflammatory effects associated with atherosclerosis and autoimmunity [60].…”