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Department of Nutrition, University of California, Davis, California 95616; and Department of Medicine, Lund University, S-20502 Malmö, Sweden
Evidence
for regulation of circulating leptin by insulin is conflicting.
Diabetes was induced in rats with streptozotocin (STZ; 40 mg · kg
1 · day1 × 2 days) to examine the effect of insulin-deficient diabetes and
insulin treatment on circulating leptin. After 12 wk, plasma leptin
concentrations in untreated rats were all <0.4 ng/ml versus 4.9 ± 0.9 ng/ml in control animals (P < 0.005). In rats treated with subcutaneous insulin implants for 12 wk,
which reduced hyperglycemia by ~50%, plasma leptin was 2.1 ± 0.6 ng/ml, whereas leptin concentrations were 6.0 ± 1.6 ng/ml in
insulin-implanted rats receiving supplemental injections of insulin for
4 days to normalize plasma glucose (P < 0.005 vs. STZ untreated). In a second experiment, plasma leptin was
monitored at biweekly intervals during 12 wk of diabetes. In rats
treated with insulin implants, plasma leptin concentrations were
inversely proportional to glycemia (r = 
0.64; P < 0.0001) and unrelated to body weight (P = 0.40). In a third experiment, plasma leptin concentrations were
examined very early after the induction of diabetes. Within 24 h after
STZ injection, plasma insulin decreased from 480 ± 30 to 130 ± 10 pM (P < 0.0001), plasma glucose increased from 7.0 ± 0.2 to 24.8 ± 0.5 mM,
and plasma leptin decreased from 3.2 ± 0.2 to 1.2 ± 0.1 ng/ml
(
= 63 ± 3%, P < 0.0001). In a subset of diabetic rats treated with insulin for 2 days,
glucose decreased to 11.7 ± 3.9 mM and leptin increased from 0.5 ± 0.1 to 2.9 ± 0.6 ng/ml (P < 0.01) without an effect on epididymal fat weight. The change of
leptin was correlated with the degree of glucose lowering
(r = 0.75, P < 0.05). Thus insulin-deficient
diabetes produces rapid and sustained decreases of leptin that are not
solely dependent on weight loss, whereas insulin treatment reverses the
hypoleptinemia. We hypothesize that decreased glucose transport into
adipose tissue may contribute to decreased leptin production in
insulin-deficient diabetes.
glucose; C-peptide; food intake; epididymal fat
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