Article

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.

0 Bookmarks
 · 
61 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: This study was made to investigate the antihyperglycemic and antioxidant potential of oil of seeds of Brassica nigra (BNO) in streptozotocin -nicotinamide (STZ) induced type 2 diabetic rats. Methods: BNO was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic study. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin and antioxidant parameters were estimated for all treated groups and compared against diabetic control group. Results: Administration of BNO at a dose 500 mg/kg and 1000 mg/kg body weight p.o. to STZ diabetic rats showed reduction in blood glucose level from 335 mg/dl to 280 mg/dl at 4th h and from 330 mg/dl to 265 mg/dl respectively which was found significant (p<0.01) as compared with diabetic control. BNO (500 mg/kg and 1000 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin-nicotinamide induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in glycosylated hemoglobin in test groups as compared to control group. In vivo antioxidant studies on STZ-nicotinamide induced diabetic rat's revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH). Conclusion: Thus the results showed that the oil of seeds of Brassica nigra has significant antihyperglycemic and antioxidant activity.
    Advanced Pharmaceutical Bulletin 01/2013; 3(2):359-365. · 0.88 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A phenomenological mathematical model for predicting FFA-glucose-insulin dynamics during rest and exercise was developed. The dynamical effects of insulin on glucose and FFA were divided into three parts: (i) insulin-mediated glucose uptake by tissues, (ii) insulin-mediated suppression of endogenous glucose production, and (iii) anti-lipolytic effects of insulin. Labeled and unlabeled intravenous glucose tolerance test data were used to estimate the parameters of the glucose model, which facilitated separation of insulin action on glucose utilization and production. The model successfully captured the FFA-glucose interactions at the systemic level. The model also successfully predicted mild-to-moderate exercise effects on FFA, glucose, and insulin dynamics. Model predictions of FFA, glucose and insulin profiles were validated with existing literature data. This composite model provides a new test platform for the development of closed-loop glucose control algorithms.
    American Control Conference (ACC), 2010; 06/2010
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to assess the relationship between serum concentrations of several persistent organic pollutants and insulin resistance markers in a cohort of women with a history of gestational diabetes mellitus. ∑POPs was computed as the sum of individual serum POP concentrations. No statistically significant associations were found between levels of any POP and fasting glucose. However, polychlorinated biphenyl (PCB) congeners 138 and 180 were positively associated with 2-h glucose levels and PCB 180 also with fasting immunoreactive insulin (IRI). We also found a positive association of p,p'- dichlorodiphenyldichloroethylene (p,p'- DDE), PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs with 2-h IRI. Serum concentrations of PCBs (138, 153, and 180), hexachlorobenzene, and ∑POPs were also positively associated with homeostasis model assessment (HOMA2-IR) levels. Moreover, p,p'- DDE, PCBs (138, 153 and 180), hexachlorobenzene, and ∑POPs were negatively associated with Insulin Sensitivity Index (ISI-gly) levels. No significant association was found between glycated hemoglobin and the concentrations of any POP. The removal of women under blood glucose lowering treatment from the models strengthened most of the associations previously found for the whole population. Our findings suggest that exposure to certain POPs is a modifiable risk factor contributing to insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.
    Environmental Research 11/2014; 136C:435-440. · 3.95 Impact Factor