Heimburger Sebastian M N, Nielsen Chris N, Calanna Salvatore, Holst Jens J, Vilsbøll Tina, Knop Filip K, Christensen Mikkel B
Centre for Clinical Metabolic Research, Copenhagen University Hospital - Herlev and Gentofte, Hellerup, Denmark.
Steno Diabetes Centre Copenhagen, Gentofte, Denmark.
Diabetes Obes Metab. 2022 Jan;24(1):142-147. doi: 10.1111/dom.14545. Epub 2021 Sep 20.
Glucose-dependent insulinotropic polypeptide (GIP) plays an important role in the glucose and lipid metabolism. We investigated the effects of exogenous GIP on lipid metabolism during time of stable insulin levels. Ten male patients with type 1 diabetes without endogenous insulin secretion (C-peptide-negative, mean [±SD] age 26 ± 4years, body mass index 24 [±2] kg/m , glycated haemoglobin 56 [±8] mmol/mol or 7.3 [±0.8]%) were studied in a randomized, double-blind, placebo-controlled, crossover study with continuous intravenous infusions of GIP (4 pmol/kg/min) or placebo (saline), during two separate 90-minute hyperglycaemic (12 mmol/L) clamps with basal insulin substitution (0.1-0.2 mU/kg/min). Plasma glycerol concentrations increased from baseline during GIP infusion and decreased during placebo infusion (baseline-subtracted area under the curve [bsAUC] 703 ± 407 vs. -262 ± 240 μmol/L × min, respectively; P < 0.001). Free fatty acids (FFAs) increased during GIP infusions (bsAUC 5505 ± 2170 μEq/L × min) and remained unchanged during placebo infusion (bsAUC -74 ± 2363 μEq/L × min), resulting in a significant difference between GIP and placebo infusions (P < 0.001). Plasma concentrations of glucose, insulin, glucagon-like peptide-1 and glucagon were similar during GIP and placebo infusions. GIP increased plasma glycerol and FFAs in patients with type 1 diabetes during hyperglycaemia and stable basal insulin levels. This supports a direct lipolytic effect of GIP at high glucose and low levels of plasma insulin.
葡萄糖依赖性促胰岛素多肽（GIP）在葡萄糖和脂质代谢中起重要作用。我们研究了在胰岛素水平稳定期间外源性GIP对脂质代谢的影响。在一项随机、双盲、安慰剂对照、交叉研究中，对10名无内源性胰岛素分泌的1型糖尿病男性患者（C肽阴性，平均[±标准差]年龄26±4岁，体重指数24[±2]kg/m²，糖化血红蛋白56[±8]mmol/mol或7.3[±0.8]%）进行了研究，在两次单独的90分钟高血糖（12 mmol/L）钳夹期间，持续静脉输注GIP（4 pmol/kg/min）或安慰剂（生理盐水），同时进行基础胰岛素替代（0.1 - 0.2 mU/kg/min）。在输注GIP期间，血浆甘油浓度从基线升高，而在输注安慰剂期间降低（曲线下面积减去基线[bsAUC]分别为703±407与 - 262±240 μmol/L×min；P < 0.001）。在输注GIP期间游离脂肪酸（FFAs）增加（bsAUC 5505±2170 μEq/L×min），而在输注安慰剂期间保持不变（bsAUC - 74±2363 μEq/L×min），导致GIP和安慰剂输注之间存在显著差异（P < 0.001）。在输注GIP和安慰剂期间，血浆葡萄糖、胰岛素、胰高血糖素样肽 - 1和胰高血糖素的浓度相似。在高血糖和基础胰岛素水平稳定的1型糖尿病患者中，GIP增加了血浆甘油和FFAs。这支持了GIP在高血糖和低血浆胰岛素水平时的直接脂解作用。
