Effect Of Aging on Glucose Oxidation and Insulin Resistance in Diaphragm in Congenic Obese Rats

Abstract

The purpose of the current investigation was to determine the characteristics of glucose oxidation in diaphragm muscle in aging congenic, lean and obese rats from 4 to 24 months of age. Insulin resistance (IR) in the diaphragm muscle is a condition where the muscle may become less responsive to insulin, thereby impairing glucose uptake and potentially contributing to diaphragmatic weakness and respiratory dysfunction. Thus, IR may become a contributor to insulin resistance in muscle and adipose tissue depots particularly in conditions like obesity and type 2 diabetes (T2DM/NIDDM). While peripheral skeletal musculature groups often represents a primary locale of IR, the ongoing physiologic contractile activity of the diaphragm may escape much of the early impact of IR since it remains a more physiologically active muscle group than skeletal muscle throughout the lifespan in man and animals, and which may confer a measure of metabolic protection from more extensive features of IR. Groups of lean and obese female littermate LA/Ntul//-cp rats, a rodent model where obesity occurs independently of NIDDM were studied at 4, 14, and 24 months of age. Parameters of IR and glucose oxidation in diaphragm determined in the presence or absence of insulin (100 μU/ml; Medium glucose 10 mM). Relative adiposity was computed by the addition of the sum of dorsal and retroperitoneal adipose tissue depots as a proportion of final body weight. Body weight of lean animals was similar at all ages studied, while body weight of obese rats increased at each successive age studied in the obese phenotype. Fasting plasma glucose concentrations were similar in both phenotypes at all ages studied, but plasma insulin concentrations and the insulin: glucose ratios were markedly elevated in the obese phenotype. animals were markedly elevated, with only modest age-related improvement. Measures of glucose oxidation in diaphragm were consistent with age related decreases in baseline and insulin stimulated glucose oxidation in the lean phenotype. In contrast, baseline and insulin- stimulated glucose oxidation in the obese phenotype were consistent with IR. These results suggest that the capacity for insulin-stimulated glucose oxidation becomes decreased in aging, with further decreases in the obese phenotype.