Contribution of hepatic and extrahepatic insulin resistance to the pathogenesis of impaired fasting glucose - Role of increased rates of gluconeogenesis
Contribution of hepatic and extrahepatic insulin resistance to the pathogenesis of impaired fasting glucose - Role of increased rates of gluconeogenesis
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DOI：
10.2337/db06-1776
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发表时间：
2007-06-01
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：
Bock, Gerlies;Chittilapilly, Elizabeth;Rizza, Robert A.
研究设计和方法：测定31例空腹血糖受损（IFG）和28例空腹血糖正常（NFG）受试者的内源性葡萄糖生成（EGP）和葡萄糖处理在禁食过夜后和钳夹期间，当内源性分泌被生长抑素和胰岛素以接近门静脉的速率输注抑制时，空腹过夜后IFG受试者的胰岛素浓度（类似于80 pmol/l，“餐前”）或进食后30分钟内（类似于300 pmol/l，“餐时”）。（P < 0.001）胰岛素和C肽浓度和内脏脂肪空腹EGP和葡萄糖代谢在IFG组和NFG组间无显著性差异（P> 0.05），提示肝内和肝外胰岛素抵抗。这在餐前得到证实。IFG组胰岛素输注量低于NFG组（P < 0.05），EGP高于NFG组（P < 0.05）。IFG组EGP增高与肿瘤发生率增高有关（P < 0.05）。在餐时胰岛素输注过程中，IFG和NFG组的EGP均受到抑制，表明肝脏胰岛素抵抗较轻。葡萄糖处置仍然较低（P < 0.01），在IFG比NFG subjects.CONCLUSIONS-Hepatic和extrahepatic胰岛素抵抗有助于空腹高血糖症IFG与前者是由于至少部分受损的胰岛素诱导的抑制血管生成。然而，由于肝脏胰岛素抵抗是轻度的，并且在进食30分钟内，在IFG受试者中通常存在的门静脉胰岛素浓度下发生EGP的接近最大抑制，因此肝外（而不是肝）胰岛素抵抗加上伴随的胰岛素分泌缺陷是餐后高甘油血症的主要原因。
OBJECTIVE-To determine the contribution of hepatic insulin resistance to the pathogenesis of impaired fasting glucose (IFG).RESEARCH DESIGN AND METHODS-Endogenous glucose production (EGP) and glucose disposal were measured in 31 subjects with IFG and 28 subjects with normal fasting glucose (NFG) after an overnight fast and during a clamp when endogenous secretion was inhibited with somatostatin and insulin infused at rates that approximated portal insulin concentrations present in IFG subjects after an overnight fast (similar to 80 pmol/l, "preprandial") or within 30 inin of eating (similar to 300 pmol/l, "prandial").RESULTS-Despite higher (P < 0.001) insulin and C-peptide concentrations and visceral fat (P < 0.05), fasting EGP and glucose disposal did not differ between IFG and NFG subjects, implying hepatic and extrahepatic insulin resistance. This was confirmed during preprandial. insulin infusion when glucose disposal was lower (P < 0.05) and EGP higher (P < 0.05) in IFG than in NFG subjects. Higher EGP was due to increased (P < 0.05) rates of gluconeogenesis in IFG. EGP was comparably suppressed in IFG and NFG groups during prandial insulin infusion, indicating that hepatic insulin resistance was mild. Glucose disposal remained lower (P < 0.01) in IFG than in NFG subjects.CONCLUSIONS-Hepatic and extrahepatic insulin resistance contribute to fasting hyperglycemia in IFG with the former being due at least in part to impaired insulin-induced suppression of gluconeogenesis. However, since hepatic insulin resistance is mild and near-maximal suppression of EGP occurs at portal insulin concentrations typically present in IFG subjects within 30 min of eating, extrahepatic (but not hepatic) insulin resistance coupled with accompanying defects in insulin secretion is the primary cause of postprandial hyperglycernia.