The effect of small increases in blood glucose on insulin secretion and endogenous glucose production in humans

IF 6.2 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Diabetes Pub Date : 2024-11-07 DOI:10.2337/db24-0388
Clinton R. Bruce, Teddy Ang, Jason D. Toms, Giang M. Dao, Jean Liu, Glenn M. Ward, David N. O’Neal, Dale J. Morrison, Greg M. Kowalski
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Abstract

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 (FFA) 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.
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血糖小幅升高对人体胰岛素分泌和内源性葡萄糖生成的影响
微小的血糖增量(≤0.5 毫摩尔/升)可对内源性葡萄糖生成(EGP)产生抑制作用,但目前还不清楚这是一个依赖于胰岛素还是独立于胰岛素的过程。在此,我们对未患糖尿病的对照组参与者和 1 型糖尿病(T1D)患者进行了低速率葡萄糖输注,以更好地了解这一现象。在 1 毫克/千克/分钟的葡萄糖输注过程中(90 分钟),葡萄糖动力学、激素和代谢物进行了测量。胰岛素浓度和分泌量迅速增加 20%,导致 EGP 抑制 40%,而葡萄糖排出量保持不变。游离脂肪酸(FFA)和胰高血糖素在 60 分钟内逐渐被抑制至比基线低 30%。在基础胰岛素浓度恒定的情况下,对患有 T1D 的参与者再次输注葡萄糖时,葡萄糖输注仅导致部分和短暂的 EGP 抑制,因此葡萄糖以近乎线性的方式增加,在 90 分钟时达到比基线高 2 mmol/L 的水平。脂肪酸和胰高血糖素保持不变,而葡萄糖排出量则略有增加。这表明,微小的血糖增量会对胰岛素分泌产生微妙的刺激作用,从而对肝脏和脂肪组织产生强大的代谢作用。可以想象,微小的血糖增加有可能成为β细胞适应的信号。
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来源期刊
Diabetes
Diabetes 医学-内分泌学与代谢
CiteScore
12.50
自引率
2.60%
发文量
1968
审稿时长
1 months
期刊介绍: Diabetes is a scientific journal that publishes original research exploring the physiological and pathophysiological aspects of diabetes mellitus. We encourage submissions of manuscripts pertaining to laboratory, animal, or human research, covering a wide range of topics. Our primary focus is on investigative reports investigating various aspects such as the development and progression of diabetes, along with its associated complications. We also welcome studies delving into normal and pathological pancreatic islet function and intermediary metabolism, as well as exploring the mechanisms of drug and hormone action from a pharmacological perspective. Additionally, we encourage submissions that delve into the biochemical and molecular aspects of both normal and abnormal biological processes. However, it is important to note that we do not publish studies relating to diabetes education or the application of accepted therapeutic and diagnostic approaches to patients with diabetes mellitus. Our aim is to provide a platform for research that contributes to advancing our understanding of the underlying mechanisms and processes of diabetes.
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