Postprandial whole-body glycolysis is similar in insulin-resistant and insulin-sensitive non-diabetic humans

Abstract

Aims/hypothesis Insulin resistance is characterised by impaired glucose utilisation when measured by a euglycaemic–hyperinsulinaemic clamp. We hypothesised that, in response to postprandial conditions, non-diabetic individuals would have similar intracellular glycolytic and oxidative glucose metabolism independent of the degree of insulin resistance. Methods Fourteen (seven male) sedentary, insulin-sensitive participants (mean±SD: BMI 25±4 kg/m2; age 39±10 years; glucose disposal rate 9.4±2.1 mg [kg estimated metabolic body size]−1 min−1) and 14 (six male) sedentary, non-diabetic, insulin-resistant volunteers (29±4 kg/m2; 34±13 years; 5.3±1.2 mg [kg estimated metabolic body size]−1 min−1) received after a 10 h fast 60 g glucose plus 15 g [6,6-2H2]glucose. Serum glucose and insulin concentrations, plasma 2H enrichment and whole-body gas exchange were determined before glucose ingestion and hourly thereafter for 4 h. Plasma 2H2O production is an index of glycolytic disposal. On day 2, participants received a weight-maintenance diet. On day 3, a euglycaemic–hyperinsulinaemic clamp was performed. Results Insulin-resistant individuals had about a twofold higher postprandial insulin response than insulin-sensitive individuals (p=0.003). Resting metabolic rate was similar in the two groups before (p=0.29) and after (p=0.33–0.99 over time) glucose ingestion, whereas a trend for blunted glucose-induced thermogenesis was observed in insulin-resistant vs insulin-sensitive individuals (p=0.06). However, over the 4 h after the 75 g glucose ingestion, glycolytic glucose disposal was the same in insulin-sensitive and insulin-resistant individuals (36.5±3.7 and 36.2±6.4 mmol, respectively; p=0.99). Similarly, whole-body carbohydrate oxidation did not differ between the groups either before or after glucose ingestion (p=0.41). Conclusions/interpretation Postprandial hyperinsulinaemia and modest hyperglycaemia overcome insulin resistance by enhancing tissue glucose uptake and intracellular glucose utilisation.

Failure of hyperglycemia and hyperinsulinemia to compensate for impaired metabolic response to an oral glucose load

“…These observations, along with those currently presented, are in contrast to a recent study using an analogous method, ingesting 2 H-labeled glucose and measuring appearance of labeled 2 H 2 O in total body water (21). In that study of 28 healthy men and women, divided into insulin resistant versus insulin sensitive subgroups by the median clamp-derived measure of insulin-stimulated glucose disposal, there was no significant difference in the rate of appearance of tracer in body water by insulin resistance status.…”

“…Our group demonstrated using limb balance methods in humans that the net glucose delivery to skeletal muscle under steady-state conditions did not differ across insulin resistance groupings, suggesting that hyperinsulinemia was sufficient to compensate for this aspect of glucose handling (20). In a recent paper, Galgani and Ravussin (21) studied integrated whole-body glucose metabolism, measuring total carbohydrate oxidation by indirect calorimetry and production of labeled water following ingestion of labeled glucose as part of a traditional 75 gram glucose load. Nondiabetic subjects were studied, divided by clamp-derived insulin sensitivity into insulin resistant and insulin sensitive groups.…”

Potential role of skeletal muscle glucose metabolism on the regulation of insulin secretion

“…In addition, a modestly higher but significant glycaemia was also detected in the insulin‐resistant versus insulinsensitive group. However, whole‐body glycolytic and glucose oxidative rates were similar among groups (Fig. ).…”

“…In the last years, we have focused our interest in the study of glucose metabolism in insulin‐sensitive and insulin‐resistant individuals under fasting, postprandial and insulin‐infused conditions . We observed that during a euglycaemic–hyperinsulinaemic clamp, both impaired intracellular oxidative and non‐oxidative glucose disposal were mostly consequence of insulin resistance .…”

Detección de la alteración del metabolismo glucídico y resistencia a la insulina en una muestra piloto infantil: Aproximación metabolómica

“…En un estado de RI, la acción de esta hormona a nivel celular está reducida, aumentando la secreción de insulina. Esto permite compensar el defecto en la acción tisular y así mantener la homeostasis glicémica (5) . Este fenómeno da cuenta del estado hiperinsulinémico, el cual es característico en sujetos con RI.…”