The Effect of Small Increases in Blood Glucose on Insulin Secretion and Endogenous Glucose Production in Humans

Small glycemic increments (≤0.5 mmol/L) can exert suppressive actions on endogenous glucose production (EGP); however, it is unclear if this is an insulin-dependent or -independent process. Here, we performed a low-rate glucose infusion in control participants without diabetes and in people with type 1 diabetes (T1D) to better understand this phenomenon. Glucose kinetics, hormones, and metabolites were measured during a 1 mg/kg/min glucose infusion (90 min), which rapidly increased glucose by ∼0.3 mmol/L in control participants. Insulin concentrations and secretion quickly increased by ∼20%, resulting in a ∼40% suppression of EGP, while glucose disposal remained unchanged. Free fatty acids (FFAs) and glucagon were gradually suppressed to ∼30% below baseline at 60 min. When repeated under constant basal insulin concentrations in participants with T1D, glucose infusion caused only partial and transient EGP suppression; hence, glucose increased in a near-linear manner, reaching levels ∼2 mmol/L above baseline at 90 min. FFAs and glucagon remained unchanged, while glucose disposal modestly increased. This demonstrates that small glycemic increments exert subtle stimulatory effects on insulin secretion that have potent metabolic actions on the liver and adipose tissue. It is conceivable that subtle increases in glucose could potentially serve as a signal for β-cell adaptation.

Small glycemic increments (≤0.5 mmol/L [≤9 mg/dL]) can suppress endogenous glucose production (EGP), but it is unclear if this depends on insulin. We conducted a low-rate glucose infusion in control participants and people with type 1 diabetes to determine the metabolic impact of minor glucose elevations and their reliance on insulin secretion. Healthy β-cells responded to subtle blood glucose elevations with small, physiologically relevant increases in insulin secretion that suppress EGP and lipolysis without stimulating glucose disposal. Small glycemic increments exerted potent insulin-dependent effects on liver and adipose tissue metabolism and could potentially serve as a β-cell adaptation signal.