This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wellhoener, P. Articles by Peters, A. Search for Related Content PubMed PubMed Citation Articles by Wellhoener, P. Articles by Peters, A.

Glucose Metabolism Rather Than Insulin Is a Main Determinant of Leptin Secretion in Humans

Departments of Internal Medicine I (P.W., B.F.-S., W.K., D.D., H.L.F., A.P.) and Clinical Neuroendocrinology (J.B.), University of Lubeck, 23538 Lubeck; and Department of Diabetes and Metabolical Disorders, Klinikum Karlsburg (W.K.), Karlsburg 17495, Germany

Address all correspondence and requests for reprints to: Peter Wellhoener, M.D., Medical University Lubeck, Department of Internal Medicine I, 23538 Lubeck, Germany.

Circulating plasma insulin and glucose levels are thought to be major regulators of leptin secretion. There is evidence from in vitro and animal experiments that glucose metabolism rather than insulin alone is a main determinant of leptin expression. Here, we tested the hypothesis that in humans also leptin secretion is primarily regulated by glucose uptake and only secondarily by plasma insulin and glucose. In 30 lean and healthy men we induced 4 experimental conditions by using the blood glucose clamp technique. A total of 60 hypoglycemic and euglycemic clamps, lasting 6 h each, were performed. During these clamps insulin was infused at either high (15.0 mU/min·kg) or low (1.5 mU/min·kg) rates, resulting in low-insulin-hypo, high-insulin-hypo, low-insulin-eu, and high-insulin-eu conditions. Serum leptin increased from 0–360 min by 20.5 ± 4.1% in the low-insulin-hypo, 33.6 ± 7.6% in the high-insulin-hypo, 39.6 ± 6.0% in the low-insulin-eu, and 60.4 ± 7.6% in the high-insulin-eu condition. Multiple regression analysis revealed a significant effect of circulating insulin (low vs. high insulin; P = 0.001) and blood glucose (hypoglycemia vs. euglycemia; P = 0.001) on the rise of serum leptin. However, when the total amount of dextrose infused during the clamp (grams of dextrose per kg BW) was included into the regression model, this variable was significantly related to the changes in serum leptin (P = 0.001), whereas circulating insulin and glucose had no additional effect. These findings in humans support previous in vitro data that leptin secretion is mainly related to glucose metabolism.

This article has been cited by other articles:

				S. H. Adams, K. L. Stanhope, R. W. Grant, B. P. Cummings, and P. J. Havel Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus Macaques Endocrinology, June 1, 2008; 149(6): 3002 - 3008. [Abstract] [Full Text] [PDF]

				P. J. Oort, T. A. Knotts, M. Grino, N. Naour, J.-P. Bastard, K. Clement, N. Ninkina, V. L. Buchman, P. A. Permana, X. Luo, et al. {gamma}-Synuclein Is an Adipocyte-Neuron Gene Coordinately Expressed with Leptin and Increased in Human Obesity J. Nutr., May 1, 2008; 138(5): 841 - 848. [Abstract] [Full Text] [PDF]

				A.K. Ludwig, J.M. Weiss, S. Tauchert, T. Dietze, S. Rudolf, K. Diedrich, A. Peters, and K.M. Oltmanns Influence of hypo- and hyperglycaemia on plasma leptin concentrations in healthy women and in women with polycystic ovary syndrome Hum. Reprod., June 1, 2007; 22(6): 1555 - 1561. [Abstract] [Full Text] [PDF]

				M J Moreno-Aliaga, M M Swarbrick, S Lorente-Cebrian, K L Stanhope, P J Havel, and J A Martinez Sp1-mediated transcription is involved in the induction of leptin by insulin-stimulated glucose metabolism J. Mol. Endocrinol., May 1, 2007; 38(5): 537 - 546. [Abstract] [Full Text] [PDF]

				M. J. Jurczak, A. M. Danos, V. R. Rehrmann, M. B. Allison, C. C. Greenberg, and M. J. Brady Transgenic overexpression of protein targeting to glycogen markedly increases adipocytic glycogen storage in mice Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E952 - E963. [Abstract] [Full Text] [PDF]

				S. C. Griffen, K. Oostema, K. L. Stanhope, J. Graham, D. M. Styne, N. Glaser, D. E. Cummings, M. H. Connors, and P. J. Havel Administration of Lispro Insulin with Meals Improves Glycemic Control, Increases Circulating Leptin, and Suppresses Ghrelin, Compared with Regular/NPH Insulin in Female Patients with Type 1 Diabetes J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 485 - 491. [Abstract] [Full Text] [PDF]

				P. Lofgren, I. Andersson, B. Adolfsson, B.-M. Leijonhufvud, K. Hertel, J. Hoffstedt, and P. Arner Long-Term Prospective and Controlled Studies Demonstrate Adipose Tissue Hypercellularity and Relative Leptin Deficiency in the Postobese State J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 6207 - 6213. [Abstract] [Full Text] [PDF]

				P. Perez-Matute, A. Marti, J. A. Martinez, M. P. Fernandez-Otero, K. L. Stanhope, P. J. Havel, and M. J. Moreno-Aliaga Eicosapentaenoic fatty acid increases leptin secretion from primary cultured rat adipocytes: role of glucose metabolism Am J Physiol Regulatory Integrative Comp Physiol, June 1, 2005; 288(6): R1682 - R1688. [Abstract] [Full Text] [PDF]

				M. Mars, C. de Graaf, L. C. de Groot, and F. J Kok Decreases in fasting leptin and insulin concentrations after acute energy restriction and subsequent compensation in food intake Am. J. Clinical Nutrition, March 1, 2005; 81(3): 570 - 577. [Abstract] [Full Text] [PDF]

				P. J. Havel Update on Adipocyte Hormones: Regulation of Energy Balance and Carbohydrate/Lipid Metabolism Diabetes, February 1, 2004; 53(90001): S143 - 151. [Abstract] [Full Text]

				L. De Marinis, A. Bianchi, A. Mancini, R. Gentilella, M. Perrelli, A. Giampietro, T. Porcelli, L. Tilaro, A. Fusco, D. Valle, et al. Growth Hormone Secretion and Leptin in Morbid Obesity before and after Biliopancreatic Diversion: Relationships with Insulin and Body Composition J. Clin. Endocrinol. Metab., January 1, 2004; 89(1): 174 - 180. [Abstract] [Full Text] [PDF]

				P. K. Chelikani, D. H. Keisler, and J. J. Kennelly Response of Plasma Leptin Concentration to Jugular Infusion of Glucose or Lipid Is Dependent on the Stage of Lactation of Holstein Cows J. Nutr., December 1, 2003; 133(12): 4163 - 4171. [Abstract] [Full Text] [PDF]

				B. J. Leury, L. H. Baumgard, S. S. Block, N. Segoale, R. A. Ehrhardt, R. P. Rhoads, D. E. Bauman, A. W. Bell, and Y. R. Boisclair Effect of insulin and growth hormone on plasma leptin in periparturient dairy cows Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R1107 - R1115. [Abstract] [Full Text] [PDF]

				B. Schultes, K. M. Oltmanns, W. Kern, H. L. Fehm, J. Born, and A. Peters Modulation of Hunger by Plasma Glucose and Metformin J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1133 - 1141. [Abstract] [Full Text] [PDF]

				S. S Elliott, N. L Keim, J. S Stern, K. Teff, and P. J Havel Fructose, weight gain, and the insulin resistance syndrome Am. J. Clinical Nutrition, November 1, 2002; 76(5): 911 - 922. [Abstract] [Full Text] [PDF]

				P. Marzullo, C. Buckway, K. L. Pratt, A. Colao, J. Guevara-Aguirre, and R. G. Rosenfeld Leptin Concentrations in GH Deficiency: The Effect of GH Insensitivity J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 540 - 545. [Abstract] [Full Text] [PDF]

				D. Dantz, J. Bewersdorf, B. Fruehwald-Schultes, W. Kern, W. Jelkmann, J. Born, H. L. Fehm, and A. Peters Vascular Endothelial Growth Factor: A Novel Endocrine Defensive Response to Hypoglycemia J. Clin. Endocrinol. Metab., February 1, 2002; 87(2): 835 - 840. [Abstract] [Full Text] [PDF]

				P. J. Havel Peripheral Signals Conveying Metabolic Information to the Brain: Short-Term and Long-Term Regulation of Food Intake and Energy Homeostasis Experimental Biology and Medicine, December 1, 2001; 226(11): 963 - 977. [Abstract] [Full Text] [PDF]

				G. E. Sonnenberg, G. R. Krakower, R. G. Hoffmann, D. L. Maas, M. M. I. Hennes, and A. H. Kissebah Plasma Leptin Concentrations during Extended Fasting and Graded Glucose Infusions: Relationships with Changes in Glucose, Insulin, and FFA J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4895 - 4900. [Abstract] [Full Text] [PDF]

				J. D. Brannian, S. M. Schmidt, D. O. Kreger, and K. A. Hansen Baseline non-fasting serum leptin concentration to body mass index ratio is predictive of IVF outcomes Hum. Reprod., September 1, 2001; 16(9): 1819 - 1826. [Abstract] [Full Text] [PDF]