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1 Department of Endocrinology and Metabolic Diseases, 2 Department of Clinical Chemistry, and 3 Department of Clinical Epidemiology, Leiden University Hospital, 2333 AA Leiden, The Netherlands; and 4 Department of Medicine, University of Texas Health Science Center, San Antonio, Texas 78284-7886.
We investigated the dose- and time-dependent
effect of insulin infusion on peripheral and portal plasma leptin
concentrations in normal rats. Three groups were studied:
group I: euglycemic (6 mmol/l) insulin
(6 mU · kg
1 · min1)
clamps for 0, 2, 4, 12, and 24 h; group
II: euglycemic insulin (18 mU · kg1 · min1)
clamp for 2 h; and group III:
euglycemic insulin (3 mU · kg1 · min1)
clamp for 7 days. In group III, food
intake was quantified during days
1-7. After an overnight fast, peripheral and
portal plasma leptin levels were identical (1.5 ± 0.2 and 1.6 ± 0.2 ng/ml). Insulin infusion (6 mU · kg1 · min1)
for 2 h had no effect on plasma leptin levels (1.5 ± 0.2 ng/ml). After 4 h (2.0 ± 0.2 ng/ml), 12 h (2.2 ± 0.4 ng/ml),
and 24 h (2.7 ± 0.6 ng/ml; all P < 0.05) of insulin infusion, a progressive time-related increase in
plasma leptin concentration was observed; portal vein leptin levels
rose in parallel and were similar to peripheral levels. When insulin
(18 mU · kg1 · min1)
was infused for 2 h, plasma leptin levels increased to 3.0 ± 0.3 ng/ml (P < 0.01). Seven days of
constant insulin infusion (3 mU · kg1 · min1)
resulted in a progressive increase in fasting plasma leptin and a
parallel decrease in food intake. A mean increase in plasma leptin
concentration of 1 ng/ml during the 7-day insulin infusion period was
associated with a mean decrease in food intake of 2.5 g/day
(multivariate ANOVA, P < 0.05). We
conclude that the insulin-induced rise in peripheral and portal vein
leptin levels is similar and both dose and time dependent. The inverse
relationship between plasma leptin concentration and food intake during
prolonged hyperinsulinemia, but not during short-term hyperinsulinemia,
supports the role of leptin in long-term food consumption.
insulin; insulin clamp
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