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

Gabrielsson, Johan (author): Swedish University of Agricultural Sciences,Sveriges lantbruksuniversitet,Inst för biomedicin och veterinär folkhälsovetenskap,Department of Biomedical Science and Veterinary Public Health

(creator_code:org_t)

2015
2015
English.
In: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 56, s. 1679-1690

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Abstract Subject headings

Acute nicotinic acid (NiAc) administration results in rapid reduction of plasma FFA concentrations. However, sustained NiAc exposure is associated with tolerance development resulting in return of FFA to pretreatment levels. The aim of this study was to determine whether a 12 h rectangular exposure profile (intermittent dose group) could avoid tolerance development and thereby reverse insulin resistance induced by lipid overload. FFA lowering was assessed in male Sprague Dawley (lean) and obese Zucker rats (obese) in response to a 5 h NiAc infusion, in either NiAc-naive animals or after 5 days of continuous (24 h/day) or intermittent (12 h/day) NiAc dosing (via implantable, programmable minipump). We found that intermittent dosing over 5 days preserved NiAc-induced FFA lowering, comparable to dosing in NiAc-naive animals. By contrast, following 5 days continuous administration, NiAc-induced FFA lowering was lost. The effect of intermittent NiAc infusion on insulin sensitivity was assessed in obese Zucker rats using hyperinsulinemic-isoglycemic clamps. The acute effect of NiAc to elevate glucose infusion rate (vs. saline control) was indeed preserved with intermittent dosing, while being lost upon continuous infusion. In conclusion, an intermittent but not continuous NiAc dosing strategy succeeded in retaining NiAc's ability to lower FFA and improve insulin sensitivity in obese Zucker rats.Kroon, T., A. Kjellstedt, P. Thalen, J. Gabrielsson, and N. D. Oakes.

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

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