Elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation during diet-induced insulin resistance in dogs

Springer Science and Business Media LLC - Tập 58 - Trang 2663-2670 - 2015
Josiane L. Broussard1, Cathryn M. Kolka1, Ana V. B. Castro1, Isaac Asare Bediako1, Rebecca L. Paszkiewicz1, Edward W. Szczepaniak1, Lidia S. Szczepaniak1, Kristen L. Knutson2, Stella P. Kim1, Richard N. Bergman1
1Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, USA
2Department of Medicine, University of Chicago, Chicago, USA

Tóm tắt

A normal consequence of increased energy intake and insulin resistance is compensatory hyperinsulinaemia through increased insulin secretion and/or reduced insulin clearance. Failure of compensatory mechanisms plays a central role in the pathogenesis of type 2 diabetes mellitus; consequently, it is critical to identify in vivo signal(s) involved in hyperinsulinaemic compensation. We have previously reported that high-fat feeding leads to an increase in nocturnal NEFA concentration. We therefore designed this study to test the hypothesis that elevated nocturnal NEFA are an early signal for hyperinsulinaemic compensation for insulin resistance. Blood sampling was conducted in male dogs to determine 24 h profiles of NEFA at baseline and during high-fat feeding with and without acute nocturnal NEFA suppression using a partial A1 adenosine receptor agonist. High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIRg). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIRg with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIRg. This relationship indicates that the hyperinsulinaemic compensation induced in response to high-fat feeding was prevented when the nocturnal NEFA pattern was returned to baseline. Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.

Tài liệu tham khảo

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