Vasselli Joseph R, Pi-Sunyer F Xavier, Wall Daniel G, John Catherine S, Chapman Colin D, Currie Paul J
Obesity Nutrition Research Center, Department of Medicine, Columbia University, New York, New York; and
Obesity Nutrition Research Center, Department of Medicine, Columbia University, New York, New York; and.
Am J Physiol Endocrinol Metab. 2017 Nov 1;313(5):E613-E621. doi: 10.1152/ajpendo.00111.2016. Epub 2017 Jul 18.
Insulin detemir (DET) is a basal insulin analog that, in contrast to other long-acting forms of insulin, has significant weight-gain-sparing effects in diabetic patients. We hypothesized that this effect of DET may be due to its enhanced catabolic action in the central nervous system. We investigated the long-term effects of single third ventricular (3V) microinjections of equimolar doses of DET and regular insulin in normal male rats on feeding, body weight, energy expenditure (EE), and respiratory quotient (RQ). Also, in acute testing, we assessed the ability of lower doses of DET to alter feeding, EE, and RQ when microinjected directly into the paraventricular nucleus (PVN). The anabolic peptide ghrelin served as a positive control in acute testing. 3V administration of both DET (0.5-2.0 mU) and regular insulin (2.0-8.0 mU) significantly reduced feeding and body weight over 48 and 120 h, respectively, with DET yielding greater inhibitory effects. DET also stimulated greater elevations of EE and reductions of RQ over 72 and 48 h postinjection, respectively. In acute (4 h) testing, microinjections of DET (0.5 mU) into the PVN reduced feeding, increased EE, and reduced RQ, while ghrelin (100 pmol) had the opposite effects. When administered sequentially into the PVN, DET (0.25 and 0.5 mU) reversed ghrelin-induced feeding, EE, and RQ effects. These data support the notion that the weight-sparing effect of DET is at least in part based on its central catabolic action and that enhanced EE and reduced RQ may participate in this effect.
地特胰岛素（DET）是一种基础胰岛素类似物，与其他长效胰岛素形式不同，它对糖尿病患者具有显著的避免体重增加的作用。我们推测DET的这种作用可能归因于其在中枢神经系统中增强的分解代谢作用。我们研究了在正常雄性大鼠的第三脑室（3V）单次微量注射等摩尔剂量的DET和常规胰岛素对进食、体重、能量消耗（EE）和呼吸商（RQ）的长期影响。此外，在急性试验中，我们评估了较低剂量的DET直接微量注射到室旁核（PVN）时改变进食、EE和RQ的能力。合成代谢肽胃饥饿素在急性试验中作为阳性对照。3V注射DET（0.5 - 2.0 mU）和常规胰岛素（2.0 - 8.0 mU）分别在48小时和120小时内显著减少进食和体重，DET产生的抑制作用更强。注射后72小时和48小时内，DET还分别刺激EE更大幅度升高和RQ降低。在急性（4小时）试验中，向PVN微量注射DET（0.5 mU）可减少进食、增加EE并降低RQ，而胃饥饿素（100 pmol）则产生相反的作用。当依次注射到PVN时，DET（0.25和0.5 mU）可逆转胃饥饿素诱导的进食、EE和RQ效应。这些数据支持这样的观点，即DET的体重减轻作用至少部分基于其在中枢的分解代谢作用，并且EE增加和RQ降低可能参与了这种作用。
