Intracerebroventricular administration of leptin markedly enhances insulin sensitivity and systemic glucose utilization in conscious rats

摘要: This study examines the acute, subacute (overnight), and chronic (7-day) effects of intracerebroventricular (i.c.v.) administration r-metMuLeptin on insulin sensitivity systemic glucose turnover in conscious unrestrained rats (body weight, 250 to 300 g). Under postabsorptive conditions, acute i.c.v. leptin ([AL] 10 microg bolus) did not affect tracer (3-(3)H-glucose)-determined production (GP) utilization (GU) rates during 2-hour hyperinsulinemic (2 mU x kg(-1) min(-1)) euglycemic clamp. Chronic ([CL] microg/d for 7 days) administered by osmotic pumps markedly reduced daily food consumption (P < .05), body weight basal plasma level .01). During clamp, GP was suppressed (55%) with CL .001 v vehicle pair-fed control groups). The insulin-induced increment GU significantly greater (23.3 +/- 1.8 mg(-1) than (16.9 0.2) pair-feeding (17.1 0.6, both P .001). Subacute ([SL] moderately but insignificantly decreased overnight (-18%) (-2.5 1.5 infusion rate final 60 minutes clamp 43% group .0001). SL also increased .005) .05) Thus, we conclude that has strong actions central nervous system result significant increases GU, these are achieved as early after administration.