alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

Konrad, Thomas R.; Vicini, Paolo; Kusterer, Klaus; Höflich, Angelika; Assadkhani, Afsaneh; Böhles, H.; Sewell, A. C.; Tritschler, Hans; Cobelli, Claudio; Usadel, K. H.

doi:10.2337/diacare.22.2.280

Cited by 162 publications

(100 citation statements)

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“…In 3T3-L1 adipocytes, similar results were reported with respect to the ability of LA to protect against the H 2 O 2 -induced loss of insulin-stimulated glucose uptake (21). Because therapeutic concentrations of LA fall within this micromolar range (17,18,22), it is possible that the protective effect of LA on insulin action in vitro is linked to its therapeutic effect in vivo.…”

Section: Discussionsupporting

confidence: 66%

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Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

et al. 2001

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In diabetic patients, ␣-lipoic acid (LA) improves skeletal muscle glucose transport, resulting in increased glucose disposal; however, the molecular mechanism of action of LA is presently unknown. We studied the effects of LA on basal and insulin-stimulated glucose transport in cultured rat L6 muscle cells that overexpress GLUT4. When 2-deoxy-D-glucose uptake was measured in these cells, they were more sensitive and responsive to insulin than wild-type L6 cells. LA, at concentrations ≤1 mmol/l, had only small effects on glucose transport in cells not exposed to oxidative stress. When cells were exposed to glucose oxidase and glucose to generate H 2 O 2 and cause oxidative stress, there was a marked decrease in insulinstimulated glucose transport. Pretreatment with LA over the concentration range of 10-1,000 µmol/l protected the insulin effect from inhibition by H 2 O 2 . Both the R and S isomers of LA were equally effective. In addition, oxidative stress caused a significant decrease (~50%) in reduced glutathione concentration, along with the rapid activation of the stress-sensitive p38 mitogen-activated protein kinase. Pretreatment with LA prevented both of these events, coincident with protecting insulin action. These studies indicate that in muscle, the major site of insulin-stimulated glucose disposal, one important effect of LA on the insulin-signaling cascade is to protect cells from oxidative stress-induced insulin resistance. Diabetes 50: [404][405][406][407][408][409][410] 2001

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Section: Discussionsupporting

confidence: 66%

“…More recently, it has been observed that chronic oral administration of LA exerts a small but significant effect on insulin sensitivity in patients with type 2 diabetes (17,18). Because the major action of insulin in vivo is to enhance glucose disposal via skeletal muscle glucose transport, it is likely that skeletal muscle is a primary target for LA action.…”

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confidence: 99%

Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

et al. 2001

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“…15,16 Exogenous treatment with R-ALA has also been shown previously to improve insulin-stimulated whole body and skeletal muscle glucose disposal in the insulin-resistant obese Zucker rat 15,[17][18][19] and treatment with a racemic mixture of ALA enhances whole-body glucose disposal in investigations of type 2 diabetic human subjects. [20][21][22][23] Because evidence to date indicates that the effects of CLA and R-ALA are mediated through different cellular mechanisms (the former through activation of PPARs and the latter via a reduction in oxidative stress), it was hypothesized that when CLA and R-ALA are used in combination, there would be at least an additive interaction in improving insulin-stimulated glucose transport in skeletal muscle of insulin resistant animals and humans. In this context, the purpose of the present investigation was to assess the interactions of CLA and R-ALA (at low, individually minimally effective doses, and at high, individually maximally effective doses) on whole-body glucose tolerance and insulin-stimulated glucose transport in skeletal muscle in an animal model of insulin resistance-the female obese Zucker rat.…”

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confidence: 99%

Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat

et al. 2003

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The fatty acid conjugated linoleic acid (CLA) and the antioxidant R-(؉)-␣-lipoic acid (R-ALA) individually enhance glucose tolerance and insulin action on skeletal muscle glucose transport in the insulin-resistant obese Zucker rat. To date, no study has assessed the potential interactions between these 2 interventions in treating insulin resistance. The present study was designed to determine whether chronic treatment with CLA and R-ALA in combination would enhance skeletal muscle glucose transport to a greater extent than either intervention individually. CLA, R-ALA, or a combination treatment of R-ALA and CLA were administered to female obese Zucker rats for 20 days at low or high doses. Whereas low-dose R-ALA (10 mg/kg body weight) alone did not alter muscle glucose transport, low-dose CLA (0.3 g/kg) induced a significant increase (38%, P < .05) in insulin-mediated glucose transport in epitrochlearis, but not in soleus. Low-dose combination therapy brought about the greatest enhancement of insulin-mediated glucose transport in epitrochlearis (77%) and soleus (54%), with the latter effect being associated with a 50% reduction in protein carbonyls (an index of tissue oxidative stress) and a 33% diminution in muscle triglycerides. High-dose treatments with CLA (1.5 g/kg), R-ALA (50 mg/kg), and the combination of CLA and R-ALA elicited increases in insulin-mediated glucose transport in epitrochlearis (57%, 58%, and 77%) and soleus (32%, 35%, and 54%). However, whereas the individual high-dose treatments with CLA and R-ALA reduced protein carbonyls (63% and 49%) and triglycerides (29% and 28%) in soleus, no further reductions were observed with the high-dose combination treatment groups. These findings support a significant interaction between low doses of CLA and R-ALA for enhancement of insulin action on skeletal muscle glucose transport, possibly via reductions in muscle oxidative stress and in lipid storage.

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“…In recent years, evidence has accumulated suggesting that α-LA has a wide range of benefits in the treatment of diabetes. Bitar et al [5] demonstrated that α-LA could partly ameliorate insulin resistance in type 2 diabetic rats, while others had reported additional antidiabetic effects in earlier rodent [4,6], and human studies [7]. In vitro approaches have also shown that α-LA can enhance glucose disposal in skeletal muscle [8] and adipocytes [9], and suppress hepatic gluconeogen-esis [10].…”

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α-Lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells

et al. 2006

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Aims/hypothesis: The antioxidant compound α-lipoic acid (α-LA) possesses antidiabetic and anti-obesity properties. In the hypothalamus, α-LA suppresses appetite and prevents obesity by inhibiting AMP-activated protein kinase (AMPK). Given the therapeutic potential of α-LA for the treatment of type 2 diabetes and obesity, and the importance of AMPK in beta cells, we examined the effect of α-LA on pancreatic beta cell function. Materials and methods: Isolated rat islets and MIN6 beta cells were treated acutely (15-90 min) or chronically (18-24 h) with α-LA or the known AMPK-activating compounds 5′-amino-imidazole-4-carboxamide ribonucleoside (AICAR) and metformin. Insulin secretion, the AMPK-signalling pathway, mitochondrial function and cell growth were assessed. Results: Acute or chronic treatment of islets and MIN6 cells with α-LA led to dose-dependent rises in phosphorylation of the AMPK α-subunit and acetyl CoA carboxylase. Chronic exposure to α-LA, AICAR or metformin caused a reduction in insulin secretion. α-LA inhibited the p70 s6 kinase translational control pathway, and inhibited MIN6 growth in a manner similar to rapamycin. Unlike AICAR and metformin, α-LA also acutely inhibited insulin secretion. Examination of the effect of α-LA on mitochondrial function showed that acute treatment with this compound elevated reactive oxygen species (ROS) production and enhanced mitochondrial depolarisation induced by Ca 2+ . Conclusions/ interpretation: This study is the first to demonstrate that α-LA directly affects beta cell function. The chronic effects of α-LA include AMPK activation and reductions in insulin secretion and content, and cell growth. Acutely, α-LA also inhibits insulin secretion, an effect probably involving the ROS-induced impairment of mitochondrial function.

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alpha-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes.

Abstract: Treatment of lean and obese diabetic patients with LA prevents hyperglycemia-induced increments of serum lactate and pyruvate levels and increases SG.

Cited by 162 publications

References 0 publications

Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

Protection Against Oxidative Stress—Induced Insulin Resistance in Rat L6 Muscle Cells by Micromolar Concentrations of α-Lipoic Acid

Interactions of conjugated linoleic acid and lipoic acid on insulin action in the obese Zucker rat

α-Lipoic acid regulates AMP-activated protein kinase and inhibits insulin secretion from beta cells

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