Comparison of the effects of pioglitazone and metformin on hepatic and extra-hepatic insulin action in people with type 2 diabetes
Comparison of the effects of pioglitazone and metformin on hepatic and extra-hepatic insulin action in people with type 2 diabetes
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DOI：
10.2337/db07-0827
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发表时间：
2008-01-01
期刊：
影响因子：
7.7
通讯作者：
Rizza, Robert A.
中科院分区：
文献类型：
--
作者：
Basu, Rita;Shah, Pankaj;Rizza, Robert A.
研究设计与方法：31例2型糖尿病患者随机分为吡格列酮(45 Mg)和二甲双胍(2,000 mg)治疗4个月。结果治疗前和治疗后血糖均控制在5 mm o l/L左右，胰岛素水平升高至180 pm o l/L，C肽用生长抑素抑制，胰高血糖素替代水平接近75 pg/m l，甘油维持在200 m m o l/L左右，以确保门脉血药浓度的可比性。用吡格列酮(23+/-3比24+/-2mmol.kg(-1)·min(-1))或二甲双胍(22+/-2比24+/-3mmol.kg(-1)·min(-1))治疗前后，胰岛素诱导的葡萄糖消失无差异。相反，吡格列酮增强(P<；0.01)胰岛素诱导的葡萄糖生成抑制(6.0+/-1.0vs.0.2+/-1.6mmol.kg(-1)·min(-1))和糖异生(n=11；4.5+/-0.9vs.0.8+/-1.2mmol.kg(-1).min(-1))。二甲双胍对葡萄糖生成的抑制(5.8+/-1.0vs.5.0：+/-0.8mmol.kg(-1)min(-1))或糖异生(n=9；3.7+/-0.8vs.2.6+/-0.7mmol.kg(-1).min(-1))均未改变。经吡格列酮治疗后，胰岛素诱导的游离脂肪酸抑制作用更强(P<；0.05)(0.140+/-03比0.06+/-0.01 mmol/L)，但二甲双胍治疗后胰岛素诱导的游离脂肪酸抑制作用不变(0.12：+/-0.03比0.15+/-0.07 mmol/L)。结论--因此，与二甲双胍相比，吡格列酮改善了2型糖尿病患者的肝脏胰岛素作用，部分是通过加强胰岛素诱导的糖异生抑制作用。另一方面，这两种药物在胰岛素诱导的葡萄糖摄取刺激方面具有类似的效果。
OBJECTIVE-To determine mechanisms by which pioglitazone and metformin effect hepatic and extra-hepatic insulin action.RESEARCH DESIGN AND METHODS-Thirty-one subjects with type 2 diabetes were randomly assigned to pioglitazone (45 mg) or metformin (2,000 mg) for 4 months.RESULTS-Glucose was clamped before and after therapy at similar to 5 mmol/l, insulin raised to similar to 180 pmol/l, C-peptide suppressed with somatostatin, glucagon replaced at similar to 75 pg/ml, and glycerol maintained at similar to 200 mmol/l to ensure comparable and equal portal concentrations on all occasions. Insulin-induced stimulation of glucose disappearance did not differ before and after treatment with either pioglitazone (23 +/- 3 vs. 24 +/- 2 mu mol.kg(-1).min(-1)) or metformin (22 +/- 2 vs. 24 +/- 3 mu mol.kg(-1).min(-1)). In contrast, pioglitazone enhanced (P < 0.01) insulin-induced suppression of both glucose production (6.0 +/- 1.0 vs. 0.2 +/- 1.6 mu mol.kg(-1).min(-1)) and gluconeogenesis (n=11; 4.5 +/- 0.9 vs. 0.8 +/- 1.2 mu mol.kg(-1).min(-1)). Metformin did not alter either suppression of glucose production (5.8 +/- 1.0 vs. 5.0 :+/- 0.8 mu mol.kg(-1) min(-1)) or gluconeogenesis (n = 9; 3.7 +/- 0.8 vs. 2.6 +/- 0.7 mu mol.kg(-1).min(-1)). Insulin-induced suppression of free fatty acids was greater (P < 0.05) after treatment with pioglitazone (0 .140 +/- 03 vs. 0.06 +/- 0.01 mmol/l) but unchanged with metformin (0.12 :+/- 0.03 vs. 0.15 +/- 0.07 mmol/l).CONCLUSIONS-Thus, relative to metformin, pioglitazone improves hepatic insulin action in people with type 2 diabetes, partly by enhancing insulin-induced suppression of gluconeogenesis. On the other hand, both drugs have comparable effects on insulin-induced stimulation of glucose uptake.