共 22 条
Effects of Pioglitazone on Intramyocellular Fat Metabolism in Patients with Type 2 Diabetes Mellitus
被引:64
作者:
Bajaj, Mandeep
[1
]
Baig, Rais
[1
]
Suraamornkul, Swangjit
[1
]
Hardies, Lou Jean
[1
]
Coletta, Dawn K.
[1
]
Cline, Gary W.
[2
]
Monroy, Adriana
[1
]
Koul, Shailja
[1
]
Sriwijitkamol, Apiradee
[1
]
Musi, Nicolas
[1
]
Shulman, Gerald I.
[2
]
DeFronzo, Ralph A.
[1
]
机构:
[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Diabet Div, San Antonio, TX 77030 USA
[2] Yale Univ, Dept Med, Sch Med, New Haven, CT 06520 USA
基金:
美国国家卫生研究院;
关键词:
HEPATIC INSULIN-RESISTANCE;
PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY;
GENE-EXPRESSION;
SUSTAINED REDUCTION;
ACID CONCENTRATION;
ADIPOSE-TISSUE;
PROTEIN-KINASE;
KNOCKOUT MICE;
GLUCOSE;
MUSCLE;
D O I:
10.1210/jc.2009-0911
中图分类号:
R5 [内科学];
学科分类号:
1002 ;
100201 ;
摘要:
Context: Lipotoxicity (increased tissue fat content) has been implicated in the development of muscle insulin resistance and type 2 diabetes mellitus (T2DM). Objective: The aim was to study the effect of pioglitazone on intramyocellular fat metabolism. Research Design: Twenty-four T2DM subjects (glycosylated hemoglobin = 8.3 +/- 0.4%) participated in three similar study protocols before and after 4 months of 45 mg/d pioglitazone treatment: 1) 3-h euglycemic insulin (80 mU/m(2).min) clamp with measurement of intramyocellular fat with proton nuclear magnetic resonance; 2) vastus lateralis muscle biopsy for measurement of LC-FACoAs 60 min before start of the insulin clamp; and 3) muscle biopsy for measurement of diacylglycerol 60 min before start of the insulin clamp. Results: In all three protocols, pioglitazone similarly reduced (all P < 0.05) the glycosylated hemoglobin (Delta = 0.8-1.2%), fasting plasma glucose (39-76 mg/dl), fasting free fatty acid (132-236 mu mol/liter), and increased insulin-stimulated glucose disposal (by 25-56%). Intramyocellular fat (protocol I) declined from 1.5 to 0.9% (P < 0.05) and correlated with the increase in glucose disposal rate (r = 0.65; P < 0.05). Long chain-fatty acyl-coenzyme A decreased from 12.5 to 8.1 nmol/g (P < 0.05) and correlated with the increase in disposal rate (r = 0.76; P < 0.05). Pioglitazone therapy had no effect on muscle diacylglycerol content. Conclusions: Pioglitazone improves insulin resistance in T2DM in association with mobilization of fat and toxic lipid metabolites out of muscle. (J Clin Endocrinol Metab 95: 1916-1923, 2010)
引用
收藏
页码:1916 / 1923
页数:8
相关论文