Different contribution of substrates oxidation to insulin resistance in malnourished elderly patients with cancer

Abstract

Background. The relative contribution of malnutrition and cancer to insulin resistance in elderly patients is still poorly understood. Methods. Twenty malnourished and 15 well‐nourished patients with cancer matched for age (70 ± 0.3 versus 69 ± 0.3 years; P = not significant), mean arterial blood pressure (104 ± 8 versus 107 ± 7 mm Hg; P = not significant), gender ratio (10 males/10 females versus 7 males/8 females), and sedentary life style underwent an euglycemic glucose clamp. Simultaneous infusion of 3‐DH‐glucose and indirect calorimetry allowed the authors to determine glucose turnover parameters and analyze substrates oxidation. Results. Malnourished patients displayed a reduced total body glucose metabolism (36 ± 2 versus 31 ± 3 μmol/kg of lean body mass X min P < 0.04), despite higher glucose oxidation. In the same group of patients, the authors demonstrated a significant increase in lipid oxidation and the lack of the inverse relationship between glucose and lipid oxidation (r = 0.07; P = not significant). Insulin infusion enhanced glucose oxidation and suppressed lipid oxidation, but such changes were at lower extent in malnourished patients. Conclusions. Our study confirms the presence of insulin resistance in malnourished patients and demonstrates the relative contribution of substrates oxidation to the insulin resistance itself.

Is there a role for carbohydrate restriction in the treatment and prevention of cancer?

“…This is in contrast to starvation, where the ketone bodies acetoacetate and β-hydroxybutyrate counteract proteolysis by providing energy for the brain and muscles [109]. In muscle, glucose uptake and glycogen synthesis are inhibited already at early stages of tumor progression, while fatty acid oxidation remains at normal levels or is increased [110,111]. In the latter case, more fat has to be provided from lipolysis in the adipose tissue.…”

A modulação da lipase de triacilglicerol do adipócito (ATGL) e da perilipina 1 contribui para o aumento da lipólise em pacientes caquéticos.

“…Diversos autores descrevem um quadro de resistência à insulina em animais caquéticos (Copeland et al, 1987;Gambardella et al, 1993;Lundholm et al, 1978) e especula-se que este fato contribua para o estabelecimento da caquexia (Asp et al, 2010). A ligação da insulina ao seu receptor inicia uma cascata de fosforilação, que começa com a autofosforilação de múltiplos resíduos de tirosina quinase da subunidade β do receptor de insulina e subsequente fosforilação dos substratos celulares, como o IRS-1 (Kasuga, 1993;White et al, 1985).…”