Dataset Information

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

ABSTRACT:

Aims/hypothesis

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.

Methods

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.

Results

High-fat feeding increased nocturnal NEFA and reduced insulin sensitivity, effects countered by an increase in acute insulin response to glucose (AIR(g)). Pharmacological NEFA inhibition after 8 weeks of high-fat feeding lowered NEFA to baseline levels and reduced AIR(g) with no effect on insulin sensitivity. A significant relationship emerged between nocturnal NEFA levels and AIR(g). 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.

Conclusions/interpretation

Elevated nocturnal NEFA are an important signal for hyperinsulinaemic compensation during diet-induced insulin resistance.

SUBMITTER: Broussard JL

PROVIDER: S-EPMC4591216 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Publications

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

Broussard Josiane L JL Kolka Cathryn M CM Castro Ana V B AV Asare Bediako Isaac I Paszkiewicz Rebecca L RL Szczepaniak Edward W EW Szczepaniak Lidia S LS Knutson Kristen L KL Kim Stella P SP Bergman Richard N RN

Diabetologia 20150809 11

<h4>Aims/hypothesis</h4>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 conc ...[more]

PMID: 26254577

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Project description:Study questionAre non-esterified fatty acid (NEFA) kinetics altered in women with polycystic ovary syndrome (PCOS)?Summary answerWomen with PCOS, particularly obese subjects, have dysregulated plasma NEFA kinetics in response to changes in plasma insulin and glucose levels, which are associated with insulin resistance (IR) independently of the fasting plasma NEFA levels.What is known alreadyElevated plasma NEFA levels are associated with IR in many disorders, although the homeostasis of NEFA kinetics and its relationship to IR in women with PCOS is unknown.Study design, size, durationWe prospectively compared insulin sensitivity and NEFA kinetics in 29 PCOS and 29 healthy controls women matched for BMI.Participants/materials, setting, methodsThis study was conducted in a tertiary institution. Plasma NEFA, glucose and insulin levels were assessed during a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT). Minimal models were used to assess insulin sensitivity (Si) and NEFA kinetics (i.e. model-derived initial plasma NEFA level [NEFA0], phi constant [Φ], reflecting glucose-mediated inhibition of lipolysis and measures of maximum rate of lipolysis [SFFA] and NEFA uptake from plasma [KFFA]).Main results and the role of chanceThe study provides new evidence that women with PCOS have defective NEFA kinetics characterized by: (i) lower basal plasma NEFA levels, measured directly and modeled (NEFA0), and (ii) a greater glucose-mediated inhibition of lipolysis in the remote or interstitial space (reflected by a lower affinity constant [Φ]). There were no differences, however, in the maximal rates of adipose tissue lipolysis (SFFA) and the rate at which NEFA leaves the plasma pool (KFFA). The differences observed in NEFA kinetics were exacerbated, and almost exclusively observed, in the obese PCOS subjects.Limitations, reasons for cautionOur study did not study NEFA subtypes. It was also cross-sectional and based on women affected by PCOS as defined by the 1990 National Institutes of Health (NIH) criteria (i.e. Phenotypes A and B) and identified in the clinical setting. Consequently, extrapolation of the present data to other phenotypes of PCOS should be made with caution. Furthermore, our data is exploratory and therefore requires validation with a larger sample size.Wider implications of the findingsDysfunction in NEFA kinetics may be a marker of metabolic dysfunction in nondiabetic obese women with PCOS and may be more important than simply assessing circulating NEFA levels at a single point in time for understanding the mechanism(s) underlying the IR of PCOS.Study funding/competing interest(s)This work was supported by NIH grants R01-DK073632 and R01-HD29364 to R.A.; a Career Development Award from MD Medical Group, Moscow, RF, to D.L. and Augusta University funds to Y.-H.C. RA serves as consultant to Ansh Labs, Medtronics, Spruce Biosciences and Latitude Capital. U.E., Z.A., D.L., R.M., Y.-H.C., R.C.B. and Y.D.I.C. have no competing interests to declare.Trial registration numberNot applicable.

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Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

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

Similar Datasets

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