Summary
Insulin is known to increase expression of the ob gene product leptin in adipose tissue of rodents. We determined whether insulin increases circulating leptin concentrations in humans, and whether this effect might be altered in patients with non-insulin-dependent diabetes mellitus (NIDDM). Plasma leptin concentrations were determined during an 8.5-h hyperinsulinaemic clamp (serum free insulin approximately 480 pmol/l) and during an 8.5-h infusion of physiological NaCl solution (saline) in eight normal subjects (age 51±3 years, BMI 26.3±0.6 kg/ m2, fasting plasma glucose 5.6±0.2 mmol/l) and seven patients with NIDDM (age 54±2 years, 27.0±0.9 kg/m2, 11.1±0.8 mmol/l). Fasting serum insulin level correlated with plasma leptin (r=0.72, p<0.005), even after adjusting for the percentage of body fat (p<0.005). During the insulin infusion, a significant increase in the plasma leptin concentration was observed after 6 h (37±14%; 5.2±0.8 vs 3.9±0.6 ng/ml, 6 vs 0 h, p<0.05) in the normal subjects and after 8.5 h (38±11%; 7.1±1.0 vs 5.5±0.9 ng/ml, 8.5 vs 0 h, p<0.05) in the patients with NIDDM. During the saline infusion, plasma leptin concentrations decreased significantly in the normal subjects by 11±1% (p<0.005) and in the patients with NIDDM by 14±1% (p<0.01) after 2 h. During the infusion of insulin as compared to saline, plasma leptin concentrations were 32±13 (p<0.05), 53±14 (p<0.001), 106±15 (p<0.001) and 165±21 (p<0.001)% higher at 2, 4, 6 and 8.5 h in the normal subjects, and 11±9 (p<0.05), 27±10 (p<0.05), 58±7 (p<0.001) and 106±13 (p<0.001)% higher in the patients with NIDDM, respectively. No differences were observed in plasma leptin concentrations between the normal subjects and patients with NIDDM, under any conditions. We conclude that prolonged exposure to insulin increases plasma leptin concentrations in humans implying a role for insulin in chronic but not acute regulation of plasma leptin concentrations. The decrease in plasma leptin concentrations during saline infusion was greater than that expected on the basis of change in serum insulin concentrations, suggesting that factors other than insulin also contribute to regulation of plasma leptin concentrations.
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Abbreviations
- NIDDM:
-
Non-insulin-dependent diabetes mellitus
References
Saladin R, De Vos P, Guerre-Millo M et al. (1995) Transient increase in obese gene expression after food intake or insulin administration. Nature 377: 527–529
Sinha MK, Ohannesian JP, Heiman ML et al. (1996) Nocturnal rise in leptin in lean, obese and non-insulin-dependent diabetes mellitus subjects. J Clin Invest 97: 1344–1347
Considine RV, Sinha MK, Heiman ML et al. (1996) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334: 292–295
DeFronzo RA, Tobin JD, Andres R (1979) Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 237(3): E214-E223
Desbuquois B, Aurbach GD (1971) Use of polyethylene glycol to separate free and antibody-bound peptide hormones in radioimmunoassays. J Clin Endocrinol 33: 732–738
Cole RA, Soeldner JS, Dunn PJ, Bunn HF (1978) A rapid method for the determination of glycosylated hemoglobins using high pressure liquid chromatography. Metabolism 27: 289–301
De Vos P, Saladin R, Auwerx J, Staels B (1995) Induction of ob gene expression by corticosteroids is accompanied by body weight loss and reduced food intake. J Biol Chem 270: 15958–15961
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Malmström, R., Taskinen, M.R., Karonen, S.L. et al. Insulin increases plasma leptin concentrations in normal subjects and patients with NIDDM. Diabetologia 39, 993–996 (1996). https://doi.org/10.1007/BF00403921
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DOI: https://doi.org/10.1007/BF00403921