Role of prior feeding status in mediating the effects of exercise on blood glucose kinetics

Abstract

Changes in blood glucose concentrations are underpinned by blood glucose kinetics (endogenous and exogenous glucose appearance rates and glucose disappearance rates). Exercise potently alters blood glucose kinetics and can thereby be used as a tool to control blood glucose concentration. However, most studies of exercise-induced changes in glucose kinetics are conducted in a fasted state, and therefore less is known about the effects of exercise on glucose kinetics when exercise is conducted in a postprandial state. Emerging evidence suggests that food intake prior to exercise can increase postprandial blood glucose flux compared with when meals are consumed after exercise, whereby both glucose appearance rates and disappearance rates are increased. The mechanisms underlying the mediating effect of exercise conducted in the fed versus the fasted state are yet to be fully elucidated. Current evidence demonstrates that exercise in the postprandial state increased glucose appearance rates due to both increased exogenous and endogenous appearance and may be due to changes in splanchnic blood flow, intestinal permeability, and/or hepatic glucose extraction. On the other hand, increased glucose disappearance rates after exercise in the fed state have been shown to be associated with increased intramuscular AMPK signaling via a mismatch between carbohydrate utilization and delivery. Due to differences in blood glucose kinetics and other physiological differences, studies conducted in the fasted state cannot be immediately translated to the fed state. Therefore, conducting studies in the fed state could improve the external validity of data pertaining to glucose kinetics and intramuscular signaling in response to nutrition and exercise.

Keywords: carbohydrate; flux; metabolism; physical activity; postprandial.

Figure 1.

Glucose metabolism during the fasted state. Hepatic glucose production is the main source of glucose to maintain euglycemia and fuel glucose-consuming tissues (7), with insulin being a key regulator. Glucose (blue circle) and insulin (yellow triangle). Figure was created with BioRender.com and used with permission.

Figure 2.

Postprandial glucose metabolism. Following digestion, blood glucose concentration increases by ingested glucose entering the circulation [i.e., exogenous glucose appearance (R_a)] and increased secretion of insulin from the pancreas is stimulated. Due to the postprandial rise in the insulin and the gastrointestinal-derived hormones, the liver contributes to the rate of glucose disappearance (R_d) of ingested glucose by increasing glucose uptake and suppressing hepatic glucose production. Insulin promotes glucose uptake into peripheral tissues such as muscle, which returns blood glucose to premeal concentration. Glucose (blue circle) and insulin (yellow triangle). GIP, glucose-dependent insulinotropic peptide; GLP-1, glucagon-like peptide-1. Figure was created with BioRender.com and used with permission.

Figure 3.

Second-meal phenomenon. Prior exposure to a meal delays gastric emptying of a subsequent meal with concomitant increases in gastrointestinal-derived hormones (e.g., GLP-1). This likely reduces ingested glucose entering the circulation (i.e., exogenous glucose appearance) and potentiates the early-phase insulin secretion. This potentiated insulin secretion combined with increased insulin sensitivity contributes to the further reduction in hepatic glucose production and enhanced muscle glucose uptake (R_d). Glucose (blue circle) and insulin (yellow triangle). GLP-1, glucagon-like peptide-1. Figure was created with BioRender.com and used with permission.

Figure 4.

Plasma glucose concentration (A) and rate of appearance (R_a) and disappearance (R_d) of plasma glucose (B) during rest and moderate-intensity exercise (cycling at 50% W_max) (35).

Figure 5.

Glucose metabolism during exercise. In the fasted state, the increase in rate of appearance of plasma glucose (R_a) is almost entirely due to an increase in hepatic glucose production. During exercise, GLUT4 translocation and activation facilitate muscle glucose uptake via insulin-independent mechanisms, supported by the increased blood flow to the active muscle. The rate of disappearance of plasma glucose (R_d) would mainly represent glucose utilization by working muscle. In the fed state, the gut provides glucose to the bloodstream and exogenous glucose appearance contributes to the increased glucose R_a. Glucose ingestion during exercise increases muscle glucose uptake (i.e., R_d) and markedly decreases hepatic glucose production, supported by stimulation of both contraction and insulin-mediated glucose uptake. Glucose (blue circle) and insulin (yellow triangle). GLUT4, glucose transporter isoform 4. Figure was created with BioRender.com and used with permission.

Figure 6.

Postprandial rate of appearance (R_a; exogenous and endogenous glucose appearance; A) and disappearance (R_d; B) of plasma glucose, during an oral glucose tolerance test (OGTT) after overnight fasted state or following exercise in the fed/fasted state. Phosphorylation of AMPK^Thr172 (C) and ACC^Ser79 (D) after overnight fasted state or following exercise in the fed/fasted state (35).