Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insulin-dependent diabetic individuals.

Avogaro, Angelo; Toffolo, Gianna; Miola, M.; Valerio, Anna; Tiengo, Antonio; Cobelli, Claudio; Prato, Stefano Del

doi:10.1172/jci118754

Cited by 78 publications

(57 citation statements)

References 45 publications

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“…In corroboration with previous studies in healthy subjects, we found that both skeletal muscle and adipose tissue are significant sources of lactate production in the postabsorptive state and that insulin stimulates net lactate release in both tissues (1,5,11,14,16,17,19,(21)(22)(23). The basal lactate release was, as expected, higher in skeletal muscle than in adipose tissue.…”

Section: Discussionsupporting

confidence: 92%

“…In skeletal muscle, studies using arteriovenous balance and isotope techniques have registered both increased and similar rates of skeletal muscle lactate release in type 2 diabetics compared with controls (1,5,9). In adipose tissue, comparison of lactate release with microdialysis in lean and obese men has shown impaired ability to increase lactate production following oral glucose in obese subjects (21).…”

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confidence: 99%

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Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

Qvisth¹,

Hagström-Toft²,

Moberg³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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To study the local tissue lactate production in the normal state and its possible disturbances in insulin resistance, rates of lactate release from adipose tissue (AT) and skeletal muscle (SM) were compared postabsorptively and during a hyperinsulinemic euglycemic clamp in 11 healthy nonobese and 11 insulin-resistant obese women. A combination of microdialysis, to measure interstitial lactate, and the 133 Xe clearance technique, to determine local blood flow, were used. In the controls, local blood flow increased by 40% in SM (P Ͻ 0.05) and remained unchanged in AT, whereas the interstitial-plasma difference in lactate doubled in AT (P Ͻ 0.005) and was unaffected in SM during hyperinsulinemia. In the obese, blood flow and interstitial-plasma difference in lactate remained unchanged in both tissues during hyperinsulinemia. The lactate release (mol ⅐ 100 g Ϫ1 ⅐ min Ϫ1 ) was 1.17 Ϯ 0.22 in SM and 0.43 Ϯ 0.11 in AT among the controls (P Ͻ 0.01) and 0.86 Ϯ 0.23 in SM and 0.83 Ϯ 0.25 in AT among the obese women in the postabsorptive state. During insulin infusion, lactate release in the controls increased to 1.92 Ϯ 0.26 in SM (P Ͻ 0.005) and to 1.14 Ϯ 0.22 in AT (P Ͻ 0.005) but remained unchanged in the obese women. It is concluded that AT and SM are both significant sources of lactate release postabsorptively, and AT is at least as responsive to insulin as SM. The ability to increase lactate release in response to insulin is impaired in AT and SM in insulin-resistant obese women, involving defective insulin regulation of both tissue lactate metabolism and local blood flow. microdialysis; blood flow

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Section: Discussionsupporting

confidence: 92%

mentioning

confidence: 99%

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

Qvisth¹,

Hagström-Toft²,

Moberg³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

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“…These observations suggest that the basal level of insulinemia is important in modulating the intracellular fate of the glucose taken up by peripheral tissues and that a dysfunction in basal insulin secretion may contribute to the accelerated release of FFAs and lactate (31). The latter is a preferential gluconeogenic substrate, and the former provides the energy required for driving gluconeogenesis; the final result is enhanced EGP and fasting hyperglycemia.…”

Section: Basal Insulin Secretionmentioning

confidence: 96%

Phasic Insulin Release and Metabolic Regulation in Type 2 Diabetes

2002

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Type 2 diabetes is a heterogeneous disorder due to prevalent insulin resistance associated with deficient insulin secretion or to a prevalent defect of insulin secretion associated with impaired insulin action. The definition is supported by the high frequency at which insulin resistance can be demonstrated in type 2 diabetic patients. Nonetheless, insulin resistance is not a sufficient mechanism to cause diabetes. Impaired ␤-cell function is a necessary defect in all conditions of impaired glucose regulation; however, it manifests itself in a different manner in fasting and glucose-stimulated conditions. In the fasting state, the basal insulin secretory rate increases as a function of the progressive decline in insulin action. As such, the fasting plasma insulin concentration is often taken as a marker for insulin sensitivity. After glucose challenge, a specific alteration of acute insulin release is an early and progressive defect. The latter might represent an intrinsic defect, but its continuous decline is affected by glucotoxicity and lipotoxicity. To understand the impact of ␤-cell dysfunction in type 2 diabetes on metabolic homeostasis, it is useful to consider the different phases of insulin secretion separately. Insulin secretion can be divided into basal (postabsorptive) and stimulated (postprandial) states. The former prevails during the interprandial phases and plays a major role during the overnight fast; the latter regulates glucose metabolism when carbohydrate is abundant and must be disposed of. Data in animals and humans support a crucial physiological role of first-phase insulin secretion in postprandial glucose homeostasis. This effect is primarily achieved in the liver, allowing prompt inhibition of endogenous glucose production and limiting the postprandial rise in plasma glucose level. In type 2 diabetes, loss of the early surge of insulin release is an early and quite common defect that may have a pathogenetic role in the development of postprandial hyperglycemia, possibly requiring specific therapeutic intervention. Diabetes 51 (Suppl. 1):S109 -S116, 2002

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“…The intracellularly produced lactate leaves the cell via simple diffusion and two proteins: monocarboxylate transporter (MCT) 1 and MCT4 [53]. The density of MCT1 and/or MCT4 in human skeletal muscle is elevated after endurance training [54][55][56] and resting blood lactate concentrations may be elevated in patients with type 2 diabetes [57][58][59]. One randomized controlled trial [22] reported a significant increase of MCT after resistance exercise.…”

Section: Othersmentioning

confidence: 99%

Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review

Wang

Simar

Singh

2009

Diabetes Metabolism Res

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SummaryThe aim of this investigation was to review morphological and metabolic adaptations within skeletal muscle to exercise training in adults with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). A comprehensive, systematic database search for manuscripts was performed from 1966 to March 2008 using computerized databases, including Medline, Premedline, CINAHL, AMED, EMBASE and SportDiscus. Three reviewers independently assessed studies for potential inclusion (exposure to exercise training, T2DM or IGT, muscle biopsy performed). A total of 18 exercise training studies were reviewed. All morphological and metabolic outcomes from muscle biopsies were collected. The metabolic outcomes were divided into six domains: glycogen, glucose facilitated transporter 4 (GLUT4) and insulin signalling, enzymes, markers of inflammation, lipids metabolism and so on. Beneficial adaptations to exercise were seen primarily in muscle fiber area and capillary density, glycogen, glycogen synthase and GLUT4 protein expressions. Few randomized controlled trials including muscle biopsy data existed, with a small number of subjects involved. More trials, especially robustly designed exercise training studies, are needed in this field. Future research should focus on the insulin signalling pathway to better understand the mechanism of the improvements in insulin sensitivity and glucose homeostasis in response to various modalities and doses of exercise in this cohort.

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Intracellular lactate- and pyruvate-interconversion rates are increased in muscle tissue of non-insulin-dependent diabetic individuals.

Cited by 78 publications

References 45 publications

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

Lactate release from adipose tissue and skeletal muscle in vivo: defective insulin regulation in insulin-resistant obese women

Phasic Insulin Release and Metabolic Regulation in Type 2 Diabetes

Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review

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