Bruce Clinton R, Ang Teddy, Toms Jason D, Dao Giang M, Liu Jean, Ward Glenn M, O'Neal David N, Morrison Dale J, Kowalski Greg M
Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Waurn Ponds, Victoria, Australia.
Institute for Physical Activity and Nutrition, Metabolic Research Unit, School of Medicine, Deakin University, Geelong, Waurn Ponds, Victoria, Australia.
Diabetes. 2025 Jun 1;74(6):898-906. doi: 10.2337/db24-0388.
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.
血糖的小幅升高（≤0.5毫摩尔/升）可对内源性葡萄糖生成（EGP）产生抑制作用；然而，尚不清楚这是一个依赖胰岛素还是不依赖胰岛素的过程。在此，我们对无糖尿病的对照参与者和1型糖尿病（T1D）患者进行了低速率葡萄糖输注，以更好地理解这一现象。在以1毫克/千克/分钟的速率输注葡萄糖（持续90分钟）期间测量葡萄糖动力学、激素和代谢产物，该输注使对照参与者的血糖迅速升高约0.3毫摩尔/升。胰岛素浓度和分泌迅速增加约20%，导致EGP抑制约40%，而葡萄糖处置保持不变。游离脂肪酸（FFA）和胰高血糖素在60分钟时逐渐被抑制至比基线低约30%。当在T1D患者的恒定基础胰岛素浓度下重复进行时，葡萄糖输注仅引起部分和短暂的EGP抑制；因此，血糖以近乎线性的方式升高，在90分钟时达到比基线高约2毫摩尔/升的水平。FFA和胰高血糖素保持不变，而葡萄糖处置适度增加。这表明血糖的小幅升高对胰岛素分泌产生微妙的刺激作用，对肝脏和脂肪组织具有强大的代谢作用。可以想象，血糖的微妙升高可能潜在地作为β细胞适应的信号。
血糖的小幅升高（≤0.5毫摩尔/升[≤9毫克/分升]）可抑制内源性葡萄糖生成（EGP），但尚不清楚这是否依赖胰岛素。我们对对照参与者和1型糖尿病患者进行了低速率葡萄糖输注，以确定轻微血糖升高的代谢影响及其对胰岛素分泌的依赖性。健康的β细胞对血糖的微妙升高会产生微小的、生理上相关的胰岛素分泌增加，从而抑制EGP和脂肪分解，而不刺激葡萄糖处置。血糖的小幅升高对肝脏和脂肪组织代谢产生强大的胰岛素依赖性作用，并可能潜在地作为β细胞适应信号。
