TY - JOUR
T1 - α-Lipoic acid prevents the development of glucose-induced insulin resistance in 3T3-L1 adipocytes and accelerates the decline in immunoreactive insulin during cell incubation
AU - Greene, E. L.
AU - Nelson, B. A.
AU - Robinson, K. A.
AU - Buse, M. G.
N1 - Funding Information:
Supported by National Institutes of Health grants R01 DK-02001 (to M.G.B.) and K01 HL-03710 (to E.L.G.) and a Robert Wood Johnson Minority Faculty Development Award (to E.L.G.). Bryce Nelson was supported by a Medical Scholars’ Fellowship from the American Diabetes Association and later by a Medical Scientist Training Grant (GM-08716-01) from the National Institutes of Health, US Public Health Service. Human recombinant insulin was a gift from Lilly Research Laboratories.
PY - 2001
Y1 - 2001
N2 - Oxidative stress has been implicated in glucose toxicity. We tested the hypothesis that certain antioxidants may prevent insulin-resistant glucose transport that develops in adipocytes after sustained exposure to high glucose, provided insulin is present. The antioxidant α-lipoic acid has been proposed as an insulin sensitizer. 3T3-L1 adipocytes were preincubated 18 hours in media containing insulin (0.6 nmol/L) with low (5 mmol/L) or high (25 mmol/L) glucose with or without α-lipoate, dihydrolipoate (each 0.1 to 0.5 mmol/L), or N-acetylcysteine (1 to 5 mmol/L). After extensive re-equilibration in insulin and antioxidant-free media, basal and maximally insulin-stimulated (100 nmol/L) glucose transport was measured. Insulin was quantified by radioimmunoassay. Preincubation with α-lipoate and dihydrolipoate but not N-acetylcysteine increased subsequent basal glucose transport; the effect was much smaller than that of acute maximal insulin stimulation. Preincubation in high glucose without antioxidants inhibited acutely insulin-stimulated glucose transport by 40% to 50% compared with low glucose. This down-regulation was partially or completely prevented by each antioxidant. In cell-free media, the 2 reductants, dihydrolipoate and N-acetylcysteine, rapidly decreased immunoreactive insulin, but α-lipoate was ineffective. However, during incubation with adipocytes, α-lipoate, and dihydrolipoate promoted the decline in immunoreactive insulin nearly equally. Because insulin and high glucose are synergistic in inducing insulin resistance in this model, the reduction in immunoreactive insulin probably contributed to the protective effect of the antioxidants. 3T3-L1 adipocytes efficiently metabolize α-lipoate to dihydrolipoate, which may be released into the medium. The stimulation of glucose transport by α-lipoic acid may represent redox effects in subcellular compartments that are accessible to dihydrolipoate.
AB - Oxidative stress has been implicated in glucose toxicity. We tested the hypothesis that certain antioxidants may prevent insulin-resistant glucose transport that develops in adipocytes after sustained exposure to high glucose, provided insulin is present. The antioxidant α-lipoic acid has been proposed as an insulin sensitizer. 3T3-L1 adipocytes were preincubated 18 hours in media containing insulin (0.6 nmol/L) with low (5 mmol/L) or high (25 mmol/L) glucose with or without α-lipoate, dihydrolipoate (each 0.1 to 0.5 mmol/L), or N-acetylcysteine (1 to 5 mmol/L). After extensive re-equilibration in insulin and antioxidant-free media, basal and maximally insulin-stimulated (100 nmol/L) glucose transport was measured. Insulin was quantified by radioimmunoassay. Preincubation with α-lipoate and dihydrolipoate but not N-acetylcysteine increased subsequent basal glucose transport; the effect was much smaller than that of acute maximal insulin stimulation. Preincubation in high glucose without antioxidants inhibited acutely insulin-stimulated glucose transport by 40% to 50% compared with low glucose. This down-regulation was partially or completely prevented by each antioxidant. In cell-free media, the 2 reductants, dihydrolipoate and N-acetylcysteine, rapidly decreased immunoreactive insulin, but α-lipoate was ineffective. However, during incubation with adipocytes, α-lipoate, and dihydrolipoate promoted the decline in immunoreactive insulin nearly equally. Because insulin and high glucose are synergistic in inducing insulin resistance in this model, the reduction in immunoreactive insulin probably contributed to the protective effect of the antioxidants. 3T3-L1 adipocytes efficiently metabolize α-lipoate to dihydrolipoate, which may be released into the medium. The stimulation of glucose transport by α-lipoic acid may represent redox effects in subcellular compartments that are accessible to dihydrolipoate.
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U2 - 10.1053/meta.2001.25601
DO - 10.1053/meta.2001.25601
M3 - Article
C2 - 11555840
AN - SCOPUS:0034788565
SN - 0026-0495
VL - 50
SP - 1063
EP - 1069
JO - Metabolism: Clinical and Experimental
JF - Metabolism: Clinical and Experimental
IS - 9
ER -