Fanelli C G, De Feo P, Porcellati F, Perriello G, Torlone E, Santeusanio F, Brunetti P, Bolli G B
Istituto di Medicina Interna e Scienze Endocrine e Metaboliche, Università di Perugia, Italy.
J Clin Invest. 1992 Jun;89(6):2005-13. doi: 10.1172/JCI115809.
Three studies were performed on nine normal volunteers to assess whether catecholamine-mediated lipolysis contributes to counterregulation to hypoglycemia. In these three studies, insulin was intravenously infused for 8 h (0.30 mU.kg-1.min-1 from 0 to 180 min, and 0.40 mU.kg-1.min-1 until 480 min). In study I (control study), only insulin was infused; in study II (direct + indirect effects of catecholamines), propranolol and phentolamine were superimposed to insulin and exogenous glucose was infused to reproduce the same plasma glucose (PG) concentration of study I. Study III (indirect effect of catecholamines) was the same as study II, except heparin (0.2 U.kg-1.min-1 after 80 min), 10% Intralipid (1 ml.min-1 after 160 min) and variable glucose to match PG of study II, were also infused. Glucose production (HGO), glucose utilization (Rd) [3-3H]glucose, and glucose oxidation and lipid oxidation (LO) (indirect calorimetry) were determined. In all three studies, PG decreased from approximately 4.8 to approximately 2.9 mmol/liter (P = NS between studies), and plasma glycerol and FFA decreased to a nadir at 120 min. Afterwards, in study I plasma glycerol and FFA increased by approximately 75% at 480 min, but in study II they remained approximately 40% lower than in study I, whereas in study III they rebounded as in study I (P = NS). In study II, LO was lower than in study I (1.69 +/- 0.13 vs. 3.53 +/- 0.19 mumol.kg-1.min-1, P less than 0.05); HGO was also lower between 60 and 480 min (7.48 +/- 0.57 vs. 11.6 +/- 0.35 mumol.kg-1.min-1, P less than 0.05), whereas Rd was greater between 210 and 480 min (19 +/- 0.38 vs. 11.4 +/- 0.34 mumol.kg-1.min-1, respectively, P less than 0.05). In study III, LO increased to the values of study I; between 4 and 8 h, HGO increased by approximately 2.5 mumol.kg-1.min-1, and Rd decreased by approximately 7 mumol.kg-1.min-1 vs. study II. We conclude that, in a late phase of hypoglycemia, the indirect effects of catecholamines (lipolysis mediated) account for at least approximately 50% of the adrenergic contribution to increased HGO, and approximately 85% of suppressed Rd.
对9名正常志愿者进行了三项研究，以评估儿茶酚胺介导的脂肪分解是否有助于对低血糖的对抗调节。在这三项研究中，静脉输注胰岛素8小时（0至180分钟为0.30 mU·kg⁻¹·min⁻¹，直至480分钟为0.40 mU·kg⁻¹·min⁻¹）。在研究I（对照研究）中，仅输注胰岛素；在研究II（儿茶酚胺的直接+间接作用）中，将普萘洛尔和酚妥拉明与胰岛素叠加，并输注外源性葡萄糖以重现与研究I相同的血浆葡萄糖（PG）浓度。研究III（儿茶酚胺的间接作用）与研究II相同，不同之处在于还输注了肝素（80分钟后为0.2 U·kg⁻¹·min⁻¹）、10%脂肪乳剂（160分钟后为1 ml·min⁻¹）以及可变葡萄糖以匹配研究II的PG。测定了葡萄糖生成（HGO）、葡萄糖利用率（Rd）[3-³H]葡萄糖以及葡萄糖氧化和脂质氧化（LO）（间接测热法）。在所有三项研究中，PG从约4.8 mmol/L降至约2.9 mmol/L（研究之间P=无显著性差异），血浆甘油和游离脂肪酸（FFA）在120分钟时降至最低点。此后，在研究I中，血浆甘油和FFA在480分钟时增加了约75%，但在研究II中它们比研究I低约40%，而在研究III中它们如研究I一样出现反弹（P=无显著性差异）。在研究II中，LO低于研究I（1.69±0.13对3.53±0.19 μmol·kg⁻¹·min⁻¹，P<0.05）；在60至480分钟之间HGO也较低（7.48±0.57对11.6±0.35 μmol·kg⁻¹·min⁻¹，P<0.05），而在210至480分钟之间Rd较高（分别为19±0.38对11.4±0.34 μmol·kg⁻¹·min⁻¹，P<0.05）。在研究III中，LO增加到研究I的值；在4至8小时之间，与研究II相比，HGO增加了约2.5 μmol·kg⁻¹·min⁻¹，而Rd降低了约7 μmol·kg⁻¹·min⁻¹。我们得出结论，在低血糖的后期阶段，儿茶酚胺的间接作用（介导的脂肪分解）至少占肾上腺素对HGO增加贡献的约50%，以及对Rd抑制的约85%。
