Elevated Gluconeogenesis in Aging and Lung Cancer is Related to Inflammation and Blunted Insulin‐Induced Protein Anabolism

Abstract

Cancer and aging are both accompanied by metabolic alterations leading to muscle loss that may result from an increased use of amino acids for gluconeogenesis (GNG).Methodswe measured the fractional contributions (%) of glycogen, glycerol and GNG from phosphoenolpyruvate (PEP) to 17h‐fasting endogenous glucose production (EGP), using oral 2H20 and deuterium enrichment of plasma glucose, by NMR spectroscopy. Whole‐body protein and glucose kinetics (1‐13C‐leucine and 3H3‐glucose) were measured fasting and during a subsequent hyperinsulinemic, euglycemic, isoaminoacidemic clamp in: young (Y, n=11; 27±3 y), older (O, n=13; 65±2 y) and older men with lung cancer (CA, n=9; 66±2 y).ResultsMen with CA had greater serum CRP levels and resting energy expenditure (REE) than Y and O, and a lesser clamp glucose disposal, indicating insulin resistance. EGP was elevated with aging and cancer with greater contribution from GNG: Y:37±2, O:43±2 and CA:48±4% (ANOVA p<0.05); % contribution from glycogen and glycerol did not differ. The resulting GNG flux (EGP × %GNG) correlated positively with CRP (r=0.69) and REE (r=0.61), and negatively with fat‐free mass index (r=−0.41), all p<0.05. GNG flux was related to lesser glucose uptake and protein anabolic response (r= −0.54, p=0.001) in response to insulin.ConclusionsInflammation may underlie the greater production of glucose from GNG and blunted protein anabolism. (CIHR)