Effects of phosphodiesterase inhibitor-induced insulin resistance on glucose and lipid metabolism in rats |
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| Authors: | YANG Gang-yi LI Ling Peter Chung Gangther Boden |
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| Institution: | 1. Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China;
2. Department of Verification, Chongqing Medical University, Chongqing 400010, China;
3. Medical College of Temple University, Philadelphia 19140, USA |
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| Abstract: | AIM:To investigate the effects of milrinone (a selective phosphdiesterase III inhibitor PDE3) on insulin secretion, blood glucose, plasma free fatty acids (FFA) and dose-response relationship, and assess possible effects of milrinone on glucose metabolism and insulin sensitivity in conscious rats.METHODS:The catheterized nonstressed rats were administered by the varying doses of milrinone (1, 5, 25 μmol/kg) and were compared with controls. A hyperinsulinaemic- euglycaemic clamp was established in awake rats, and milrinone(25 μmol/kg) and 25% dimethyl sulfoxide (DMSO, as a control) were given at 120 min during hyperinsulinaemic- euglycaemic clamp. Glucose turnover was decided by gas chromatograph mass spectrometer (GC-MS).RESULTS:After dosing, plasma FFA levels in 3 milrinone groups significantly increased compared with the controls and before dosing. The percentages of elevation of FFA by the different milrinone doses were very similar, 50%, 52%, 55% for 1, 5, 25 μmol/kg respectively at 2 min after dosing. Plasma insulin levels were significantly elevated in the 5 and 25 μmol/kg groups, and the effect of milrinone on glucose concentration was detectable only 25 μmol/kg group. During hyperinsulinaemic clamp, there were significant increase in plasma FFA (from 173.1±15.2 to 633.8±87.3 μEq/L) and hepatic glucose production (HGP), and a significant decrease in glucose infusion rates (GIR) (to about 21%).CONCLUSION:These data suggest that milrinone impaires the abilities of insulin to suppress lipolysis and HGP, and insulin-mediated glucose utilization in peripheral tissue. Therefore, milrinone administration may induce an acute insulin resistancein vivo. |
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| Keywords: | Milrinone Phosphodiesterase inhibitors Insulin |
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