What question did this study set out to answer?

To determine whether a 12-hour intermittent nicotinic acid dosing schedule prevents tolerance development and reverses lipid overload-induced insulin resistance compared to continuous administration.

August 28, 2015Journal of Lipid ResearchOpen Access

Dosing profile profoundly influences nicotinic acid's ability to improve metabolic control in rats

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Authors

TKTobias KroonAstraZeneca (Finland)AKAnn KjellstedtAstraZeneca (United Kingdom)PTPia ThalénFaculdade Meridional

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Implication

Animal study reveals that intermittent nicotinic acid delivery preserves lipid lowering and improves insulin sensitivity in obese rats, suggesting a way to circumvent drug tolerance.

Key Points

To determine whether a 12-hour intermittent nicotinic acid dosing schedule prevents tolerance development and reverses lipid overload-induced insulin resistance compared to continuous administration.
Administered nicotinic acid via implantable, programmable minipumps continuously (24 h/day) or intermittently (12 h/day) for 5 days, or as an acute 5-hour infusion in drug-naïve animals.
Evaluated plasma free fatty acid lowering following a 5-hour nicotinic acid infusion in male Sprague Dawley (lean) and obese Zucker rats.
Assessed insulin sensitivity in obese Zucker rats using hyperinsulinemic-isoglycemic clamps to measure glucose infusion rates relative to saline controls.
Intermittent dosing for 5 days fully preserved acute free fatty acid lowering in both lean and obese rats, matching reductions observed in drug-naïve animals.
Continuous 5-day administration induced complete tolerance, abolishing the free fatty acid-lowering efficacy of nicotinic acid.
Intermittent delivery preserved the acute ability of nicotinic acid to elevate glucose infusion rates during hyperinsulinemic-isoglycemic clamps, whereas continuous infusion completely lost this insulin-sensitizing effect.

Cite This Study

Kroon et al. (2015) studied this question.

synapsesocial.com/papers/6a8be7fa90fae8fd47e99bc8 https://doi.org/10.1194/jlr.m058149

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Implication

Animal study reveals that intermittent nicotinic acid delivery preserves lipid lowering and improves insulin sensitivity in obese rats, suggesting a way to circumvent drug tolerance.

Dosing profile profoundly influences nicotinic acid's ability to improve metabolic control in rats

Discussion

Member takes

Implication

Key Points

Cite This Study

Dosing profile profoundly influences nicotinic acid's ability to improve metabolic control in rats

Discussion

Member takes

Implication

Key Points

Cite This Study

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