Osei Kwame, Gaillard Trudy, Cook Charles, Kaplow June, Bullock Matthew, Schuster Dara
Division of Endocrinology, Diabetes and Metabolism, The Ohio State University College of Medicine and Public Health, Columbus, Ohio 43210, USA.
Ethn Dis. 2005 Autumn;15(4):641-8.
We examined the effects of rosiglitazone: 1) on glucose homeostasis, insulin action, beta-cell function, and plasma adiponectin and TNF-alpha (TNF-alpha) levels; and 2) the expression of adipose tissue TNF-alpha and adiponectin mRNA in African Americans with parental history of type 2 diabetes and with varying degrees of glucose intolerance.
The study groups comprised 11 African Americans with normal glucose tolerance and six with diabetes and impaired glucose tolerance. The glucose-intolerant subjects received rosiglitazone (4-8 mg/day) every morning for 12 weeks. They underwent oral glucose tolerance test (OGTT) and subcutaneous adipose tissue biopsy (under local anesthesia) before and after 12 weeks of rosiglitazone therapy. Beta cell function and insulin resistance were calculated by using homeostasis model assessment (HOMA). Adipose tissue gene expression (mRNA) was measured by real-time polymerase chain reaction in both groups.
Rosiglitazone monotherapy improved both fasting and two-hour serum glucose levels during OGTT in the glucose-intolerant group. However, mean serum insulin and C-peptide levels did not change when compared with baseline. Rosiglitazone monotherapy improved insulin resistance but not overall beta-cell secretion. Mean adiponectin levels at fasting and two hours after oral glucose ingestion were significantly (50%) lower in the glucose-intolerant group than in the control group. Rosiglitazone monotherapy significantly increased plasma adiponectin levels at fasting and two hours after oral challenge by two-fold in the glucose-intolerant group. Mean plasma TNF-alpha levels were not significantly different at fasting and after two hours during OGTT. Rosiglitazone had no significant effect on plasma TNF-alpha levels during OGTT. No significant differences were seen in the expression of adipose tissue TNF-alpha and adiponectin mRNA in the groups at baseline. Rosiglitazone did not significantly change the adipose tissue adiponectin and TNF-alpha mRNA. Rosiglitazone was well tolerated, without experiencing weight gain, edema, and liver function test abnormality in the glucose intolerant subjects.
Rosiglitazone improved glucose homeostasis and insulin resistance in high-risk African Americans. We found that adiponectin was lower in the glucose-intolerant group, while TNF-alpha was similar. While rosiglitazone increased plasma adiponectin, it had no effect on adipose tissue adiponectin mRNA. In addition, rosiglitazone had no effect on plasma TNF-alpha and adipose tissue TNF-alpha mRNA. We conclude that the metabolic effects of rosiglitazone could be mediated by adiponectin but not TNF-alpha in African Americans with glucose intolerance. Our study demonstrates that: 1) the role of adipocytokines in the etiology of type 2 diabetes in African Americans is complex; and 2) that adiponectin, but not TNF-alpha, could mediate the metabolic benefits of thiazolidinediones in African Americans with glucose intolerance.
我们研究了罗格列酮的作用：1）对葡萄糖稳态、胰岛素作用、β细胞功能以及血浆脂联素和肿瘤坏死因子-α（TNF-α）水平的影响；2）对有2型糖尿病家族史且葡萄糖耐量不同程度受损的非裔美国人脂肪组织TNF-α和脂联素mRNA表达的影响。
研究组包括11名葡萄糖耐量正常的非裔美国人和6名患有糖尿病及葡萄糖耐量受损的非裔美国人。葡萄糖耐量受损的受试者每天早晨服用罗格列酮（4 - 8毫克/天），持续12周。在罗格列酮治疗12周前后，他们接受了口服葡萄糖耐量试验（OGTT）和皮下脂肪组织活检（局部麻醉下）。通过稳态模型评估（HOMA）计算β细胞功能和胰岛素抵抗。两组均采用实时聚合酶链反应测量脂肪组织基因表达（mRNA）。
在葡萄糖耐量受损组中，罗格列酮单药治疗改善了OGTT期间的空腹和两小时血清葡萄糖水平。然而，与基线相比，平均血清胰岛素和C肽水平没有变化。罗格列酮单药治疗改善了胰岛素抵抗，但未改善整体β细胞分泌。葡萄糖耐量受损组空腹和口服葡萄糖后两小时的平均脂联素水平比对照组显著低50%。罗格列酮单药治疗使葡萄糖耐量受损组空腹和口服葡萄糖后两小时的血浆脂联素水平显著增加了两倍。OGTT期间空腹和两小时后的平均血浆TNF-α水平无显著差异。罗格列酮对OGTT期间的血浆TNF-α水平无显著影响。两组在基线时脂肪组织TNF-α和脂联素mRNA的表达无显著差异。罗格列酮未显著改变脂肪组织脂联素和TNF-α mRNA。在葡萄糖耐量受损的受试者中，罗格列酮耐受性良好，未出现体重增加、水肿和肝功能检查异常。
罗格列酮改善了高危非裔美国人的葡萄糖稳态和胰岛素抵抗。我们发现葡萄糖耐量受损组的脂联素较低，而TNF-α相似。虽然罗格列酮增加了血浆脂联素，但对脂肪组织脂联素mRNA没有影响。此外，罗格列酮对血浆TNF-α和脂肪组织TNF-α mRNA没有影响。我们得出结论，在葡萄糖耐量受损的非裔美国人中，罗格列酮的代谢作用可能由脂联素介导，而非TNF-α。我们的研究表明：1）脂肪细胞因子在非裔美国人2型糖尿病病因中的作用是复杂的；2）脂联素而非TNF-α可能介导了噻唑烷二酮类药物对葡萄糖耐量受损的非裔美国人的代谢益处。
