Regulation of free fatty acid metabolism by insulin in humans: Role of lipolysis and reesterification

Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-2230.
The American journal of physiology (Impact Factor: 3.28). 12/1992; 263(6 Pt 1):E1063-9.
Source: PubMed

ABSTRACT The regulation of lipolysis, free fatty acid appearance into plasma (FFA R(a)), an FFA reesterification and oxidation were examined in seven healthy humans infused intravenously with insulin at rates of 4, 8, 25, and 400 mU.m-2.min-1. Glycerol and FFA R(a) were determined by isotope dilution methods, and FFA oxidation was calculated by indirect calorimetry or by measurement of expired 14CO2 from infused [1-14C]palmitate. These measurements were used to calculate total FFA reesterification, primary FFA reesterification occurring within the adipocyte, and secondary reesterification of circulating FFA molecules. Lipolysis, FFA R(a), and secondary FFA reesterification were exquisitely insulin sensitive [the insulin concentrations that produced half-maximal suppression (EC50), 106 +/- 26, 91 +/- 20 vs. 80 +/- 16 pM, P = not significant] in contrast to insulin suppression of FFA oxidation (EC50, 324 +/- 60, all P < 0.01). The absolute rate of primary FFA reesterification was not affected by the increase in insulin concentration, but the proportion of FFA molecules undergoing primary reesterification doubled over the physiological portion of the insulin dose-response curve (from 0.23 +/- 0.06 to 0.44 +/- 0.07, P < 0.05). This served to magnify insulin suppression of FFA R(a) twofold. In conclusion, insulin regulates FFA R(a) by inhibition of lipolysis while maintaining a constant rate of primary FFA reesterification.

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    • "Onset of type 2 diabetes is commonly preceded by early metabolic changes (prediabetes), including a progressive development of insulin resistance, which is first compensated by the overproduction of insulin by beta cells until the insulin production becomes inadequate (Hsueh et al., 2010). The effects of insulin include a reduction in blood glucose and free fatty acids, the latter being derived from a suppression of lipolysis (Campbell et al., 1992). Hence, assuming equal insulin levels, higher blood glucose levels are related to lower insulin sensitivity. "
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    Environmental Research 11/2014; 136C:435-440. DOI:10.1016/j.envres.2014.11.007 · 3.95 Impact Factor
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    • "The synthesis, degradation, and transformation of FA in hepatic cells are catalyzed by over 300 enzymatic reactions (Kanehisa et al., 2008) involved in distinct pathways (e.g., FA oxidation and elongation). These reactions are regulated at the metabolic and genetic levels by various hormones (e.g., insulin (Campbell et al., 1992), leptin (Unger et al., 1999)) and nutrients (e.g., poly unsaturated FA (Sessler and Ntambi, 1998)). However, the simple aggregation of abundant literature data cannot account for all underlying interactions responsible for both FA metabolism and lipid phenotype. "
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    Journal of Theoretical Biology 08/2009; 261(2):266-78. DOI:10.1016/j.jtbi.2009.07.025 · 2.30 Impact Factor
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    • "Just as important to the regulation of fat metabolism is the involvement of insulin hormone in the regulation of FA mobilization and oxidation. Plasma NEFA reesterification is particularly sensitive to insulin action (Campbell et al., 1992), such that even low concentrations of plasma insulin can be sufficient to suppress adipose tissue lipolysis at rest (Bonadonna et al., 1990). Thus, whereas catecholamine-activated α-adrenoceptors modulate lipolysis at rest, insulin action modulates lipolysis postprandially. "
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