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Horm Metab Res 2006; 38(9): 598-602
DOI: 10.1055/s-2006-951309
Original Clinical

© Georg Thieme Verlag KG Stuttgart · New York

A Study to Determine if Acute Maternal and Fetal Hyperglycemia/Insulinemia Induces Leptin Production during Pregnancy

J. Santolaya-Forgas 1 , S. H. Mehta 2 , V. D. Castracane 3
  • 1Center for Fetal Medicine and Prenatal Genetics, Brigham and Women's Hospital Harvard Medical School, Boston, MA 02115, USA
  • 2Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Hutzel Women's Hospital, Wayne State University, Detroit, Michigan 48201, USA
  • 3Foundation for Blood Research, Scarborough, Maine 04070, USA
Further Information

Publication History

Received 2 January 2006

Accepted after revision 27 April 2006

Publication Date:
18 September 2006 (online)

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Abstract

Background: In pregnant primates, the effect of post-prandial hyperglycemic or insulinemic states on leptin production is not known. Our goal was to conduct a controlled study using an established pregnant baboon model (Papio anubis) to determine whether acute glucose changes would have an effect on maternal or fetal plasma leptin levels. Methods: Two animals were operated on at 138 and 140 days of gestation (term ∼184 days) by placing 4 cannulae in the maternal aorta, inferior vena cava, fetal carotid artery, and the amniotic cavity. At 145 and 150 days, glucose infusions were started via the maternal femoral vein. Animal 1 received 7.5 gm of glucose over a 2-hour period at 145th day. Animal 2 received 20 gm of glucose over a 1-hour period at 150th day. Both animals remained ad libitum throughout the experiments. Maternal and fetal blood samples were obtained from the arterial lines before the glucose infusion and at half hour intervals to include 30 minutes post-infusion. Results: Significant changes from baseline concentrations were observed for maternal and fetal glucose and insulin concentrations in response to both glucose challenges. Maternal and fetal plasma leptin concentrations did not correlate with glucose or insulin changes. Conclusion: This preliminary study demonstrated that in primates, acute changes in circulating maternal or fetal glucose or insulin concentration do not affect maternal or fetal plasma leptin concentrations. These results suggest that alterations in leptin secretion by the maternal-placental-fetal unit may only occur in pathological states.

Key words

Pregnancy - baboon - maternal hyperglycemia - fetal leptin

References

  • 1 Margetic S, Gazzola C, Pegg GG, Hill RA. Leptin: a review of its peripheral actions and interactions.  Int J Obes Relat Metab Disord. 2002;  26 1407-1433
    CrossrefPubMedSearch in Google Scholar
  • 2 Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals.  Nature. 1998;  395 763-770
    CrossrefPubMedSearch in Google Scholar
  • 3 Popovic V, Duntas LH. Leptin TRH and ghrelin: influence on energy homeostasis at rest and during exercise.  Horm Metab Res. 2005;  37 533-537
    Thieme ConnectPubMedSearch in Google Scholar
  • 4 Prolo P, Wong M, Licinio J. Leptin.  Int J Biochem Cell Biol. 1998;  30 1285-1290
    CrossrefPubMedSearch in Google Scholar
  • 5 Bajoria R, Sooranna SR, Ward BS, Chatterjee R. Prospective function of placental leptin at maternal-fetal interface.  Placenta. 2002;  23 103-115
    CrossrefPubMedSearch in Google Scholar
  • 6 Schubring C, Kiess W, Englaro P, Rascher W, Dotsch J, Hanitsch S, Attanasio A, Blum WF. Levels of leptin in maternal serum, amniotic fluid, and arterial and venous cord blood: relation to neonatal and placental weight.  J Clin Endocrinol Metab. 1997;  82 1480-1483
    CrossrefPubMedSearch in Google Scholar
  • 7 Laml T, Hartmann BW, Ruecklinger E, Preyer O, Soeregi G, Wagenbichler P. Maternal serum leptin concentrations do not correlate with cord blood leptin concentrations in normal pregnancy.  J Soc Gynecol Investig. 2001;  8 43-47
    PubMedSearch in Google Scholar
  • 8 Linnemann K, Malek A, Sager R, Blum WF, Schneider H, Fusch C. Leptin production and release in the dually in vitro perfused human placenta.  J Clin Endocrinol Metab. 2000;  85 4298-4301
    CrossrefPubMedSearch in Google Scholar
  • 9 Henson MC, Castracane VD. Leptin in pregnancy.  Biol Reprod. 2000;  63 1219-1228
    PubMedSearch in Google Scholar
  • 10 Okereke NC, Uvena-Celebrezze J, Hutson-Presley L, Amini SB, Catalano PM. The effect of gender and gestational diabetes mellitus on cord blood concentration.  Am J Obstet Gynecol. 2002;  187 798-803
    CrossrefPubMedSearch in Google Scholar
  • 11 Herring JM, Fortman JD, Anderson RJ, Bennett BT. Ultrasonic determination of fetal parameters in baboons (Papio anubis).  Lab Anim Sci. 1991;  41 602-605
    PubMedSearch in Google Scholar
  • 12 Henson MC, Castracane VD, O'Neil JS, Gimpel T, Swan KF, Green AE, Shi W. Serum leptin concentrations and expression of leptin transcripts in placental trophoblast with advancing baboon pregnancy.  J Clin Endocrinol Metabol. 1999;  84 2543-2549
    CrossrefPubMedSearch in Google Scholar
  • 13 Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, Ohannesian JP, Marco CC, McKee LJ, Bauer TL. et al . Serum immunoreactive-leptin concentrations in normal-weight and obese humans.  N Engl J Med. 1996;  334 292-295
    CrossrefPubMedSearch in Google Scholar
  • 14 Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK. Weight-reducing effects of the plasma protein encoded by the obese gene.  Science. 1995;  269 543-546
    CrossrefPubMedSearch in Google Scholar
  • 15 Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue.  Nature. 1994;  372 425-432
    CrossrefPubMedSearch in Google Scholar
  • 16 Emilsson V, Liu YL, Cawthorne MA, Morton NM, Davenport M. Expression of the functional leptin receptor mRNA in pancreatic islets and direct inhibitory action of leptin on insulin secretion.  Diabetes. 1997;  46 313-316
    CrossrefPubMedSearch in Google Scholar
  • 17 Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, Prunkard DE, Porte Jr D, Woods SC, Seeley RJ. et al . Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide y gene expression in ob/ob mice.  Diabetes. 1996;  45 531-535
    PubMedSearch in Google Scholar
  • 18 Zhou YT, Shimabukuro M, Koyama K, Lee Y, Wang MY, Trieu F, Newgard CB, Unger RH. Induction by leptin of uncoupling protein-2 and enzymes of fatty acid oxidation.  Proc Natl Acad Sci USA. 1997;  94 6386-6390
    CrossrefPubMedSearch in Google Scholar
  • 19 Boden G, Chen X, Kolaczynski JW, Polansky M. Effects of prolonged hyperinsulinemia on serum leptin in normal human subjects.  J Clin Invest. 1997;  100 1107-1113
    PubMedSearch in Google Scholar
  • 20 Saad MF, Khan A, Sharma A, Michael R, Riad-Gabriel MG, Boyadjian R, Jinagouda SD, Steil GM, Kamdar V. Physiological insulinemia acutely modulates plasma leptin.  Diabetes. 1998;  47 544-549
    CrossrefPubMedSearch in Google Scholar
  • 21 Utriainen T, Malmstrom R, Makimattila S, Yki-Jarvinen H. Supraphysiological hyperinsulinemia increases plasma leptin concentrations after 4 h in normal subjects.  Diabetes. 1996;  45 1364-1366
    PubMedSearch in Google Scholar
  • 22 Popovic V, Micic D, Danjanovic S, Zoric S, Djurovic M, Obradovic S, Petakov M, Dieguez C, Casanueva FF. Serum leptin and insulin concentrations in patients with insulinoma before and after surgery.  Eur J Endocrinol. 1998;  138 86-88
    CrossrefPubMedSearch in Google Scholar
  • 23 Lea R, Howe D, Hannah LT, Bonneau O, Hunter L, Hoggard N. Placental leptin in normal, diabetic and fetal growth-retarded pregnancies.  Mol Hum Reprod. 2000;  6 763-769
    CrossrefPubMedSearch in Google Scholar
  • 24 Lepercq J, Cauzac M, Lahlou N, Timsit J, Girard J, Auwerx J, Hauguel-de Mouzon S. Overexpression of placental leptin in diabetic pregnancy: a critical role for insulin.  Diabetes. 1998;  47 847-850
    CrossrefPubMedSearch in Google Scholar
  • 25 Lappas M, Yee K, Permezel M, Rice GE. Release and regulation of leptin, resistin and adiponectin from human placenta, fetal membranes, and maternal adipose tissue and skeletal muscle from normal and gestational diabetes mellitus-complicated pregnancies.  J Endocrinol. 2005;  186 457-465
    CrossrefPubMedSearch in Google Scholar
  • 26 Christou H, Serdy S, Mantzoros CS. Leptin in relation to growth and developmental processes in the fetus.  Sem Reprod Med. 2002;  20 123-129
    PubMedSearch in Google Scholar
  • 27 Nicolini U, Hubinont C, Santolaya J, Fisk NM, Coe AM, Rodeck CH. Maternal-fetal glucose gradient in normal pregnancies and in pregnancies complicated by alloimmunization and fetal growth retardation.  Am J Obstet Gynecol. 1989;  161 924-927
    PubMedSearch in Google Scholar
  • 28 Nicolini U, Hubinont C, Santolaya J, Fisk NM, Rodeck CH. Effects of fetal intravenous glucose challenge in normal and growth retarded fetuses.  Horm Metab Res. 1990;  22 426-430
    Thieme ConnectPubMedSearch in Google Scholar

Correspondence

Joaquin Santolaya-ForgasM.D., Ph.D. 

Division of Maternal-Fetal Medicine·Department of Obstetrics and Gynecology·Center for Fetal Medicine and Prenatal Genetics·Brigham and Women's Hospital Harvard Medical School

75 Francis St. Boston·MA 02115·USA

Phone: +1/617/732/42 08

Fax: +1/617/264/63 10

Email: jsantolaya@partners.org