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

Abstract

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

Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes

“…Our results demonstrate that this is the case, the amount of lactate released from a human adipocyte system in culture being markedly enhanced. Interestingly, lactate levels in white adipose tissue in rodents have been found to be increased in obesity and diabetes [4,11,20,26], conditions that are also associated with higher plasma lactate levels [16,21,46].…”

2D-DIGE to identify proteins associated with gestational diabetes in omental adipose tissue

“…In this study, we found that the b chain of LDH was decreased in adipose tissue of women with GDM. It is possibly that a deficiency in LDHB protein might contribute to impaired net lactate release from adipose tissue in response to insulin and may explain the lower plasma lactate levels that are seen in the obese women during hyperinsulinaemia (Qvisth et al 2007). …”

International Union of Basic and Clinical Pharmacology. LXXXII: Nomenclature and Classification of Hydroxy-carboxylic Acid Receptors (GPR81, GPR109A, and GPR109B)

“…The liver takes up the lactate released from adipocytes and uses it for gluconeogenesis and glycogen synthesis. Because insulin-induced glucose uptake results in a severalfold increase in extracellular lactate levels in adipose tissue (Jansson et al, 1994;Qvisth et al, 2007;Ahmed et al, 2010), the hypothesis was formulated that lactate, acting through the HCA 1 receptor, contributes to the inhibition of lipolysis induced by insulin. In fact, studies in HCA 1 receptor-deficient mice and adipocytes clearly showed that insulin-induced inhibition of lipolysis and insulin-in-HCA RECEPTOR NOMENCLATURE duced decrease in adipocyte cAMP were strongly reduced in the absence of HCA 1 .…”