دورية أكاديمية

Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog.

التفاصيل البيبلوغرافية
العنوان: Changes in Glucose and Fat Metabolism in Response to the Administration of a Hepato-Preferential Insulin Analog.
المؤلفون: Edgerton, Dale S., Moore, Mary C., Winnick, Jason J., Scott, Melanie, Farmer, Ben, Naver, Helle, Jeppesen, Claus B., Madsen, Peter, Kjeldsen, Thomas B., Nishimura, Erica, Brand, Christian L., Cherrington, Alan D.
المصدر: Diabetes; Nov2014, Vol. 63 Issue 11, p3946-3954, 9p, 2 Charts, 5 Graphs
مصطلحات موضوعية: INSULIN research, METABOLISM, FAT, GLUCOSE, GLUCAGON
مستخلص: Endogenous insulin secretion exposes the liver to three times higher insulin concentrations than the rest of the body. Because subcutaneous insulin delivery eliminates this gradient and is associated with metabolic abnormalities, functionally restoring the physiologic gradient may provide therapeutic benefits. The effects of recombinant human insulin (HI) delivered intraportally or peripherally were compared with an acylated insulin model compound (insulin-327) in dogs. During somatostatin and basal portal vein glucagon infusion, insulin was infused portally (PoHI; 1.8 pmol/kg/min; n = 7) or peripherally (PeHI; 1.8 pmol/kg/min; n = 8) and insulin-327 (Pe327; 7.2 pmol/kg/min; n = 5) was infused peripherally. Euglycemia was maintained by glucose infusion. While the effects on liver glucose metabolism were greatest in the PoHI and Pe327 groups, nonhepatic glucose uptake increased most in the PeHI group. Suppression of lipolysis was greater during PeHI than PoHI and was delayed in Pe327 infusion. Thus small increments in portal vein insulin have major consequences on the liver, with little effect on nonhepatic glucose metabolism, whereas insulin delivered peripherally cannot act on the liver without also affecting nonhepatic tissues. Pe327 functionally restored the physiologic portal-arterial gradient and thereby produced hepato-preferential effects. [ABSTRACT FROM AUTHOR]
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قاعدة البيانات: Complementary Index
الوصف
تدمد:00121797
DOI:10.2337/db14-0266