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Horm Metab Res 2001; 33(4): 207-212
DOI: 10.1055/s-2001-14947
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Effect of Leptin on Insulin, Glugacon and Somatostatin Secretion in the Perfused Rat Pancreas

R. A. Silvestre, J. Rodríguez-Gallardo, E. M. Egido, J. Marco
  • Clínica Puerta de Hierro and Department of Physiology, Universidad Autónoma de Madrid, Madrid, Spain
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Publication History

Publication Date:
31 December 2001 (online)

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We have investigated the effect of rat leptin as well as the 22 - 56 fragment of this molecule on pancreatic hormone secretion in the perfused rat pancreas. In pancreases from fed rats, leptin failed to alter the insulin secretion elicited by glucose, arginine or tolbutamide, but inhibited the insulin response to both CCK-8 and carbachol, secretagogues known to act on the B-cell by increasing phospholipid turnover. This insulinostatic effect was also observed with the 22 - 56 leptin fragment. In pancreases obtained from 24-hour fasted rats, no effect of leptin on carbachol-induced insulin output was found, perhaps as a consequence of depressed B-cell phospholipid metabolism. Leptin did not influence glucagon or somatostatin release. Our results do not support the concept of leptin as a major regulator of B-cell function. Leptin inhibition of carbachol-induced insulin output might reflect a restraining effect of this peptide on the cholinergic stimulation of insulin release.

Key words:

Rat Pancreas - Leptin - Insulin - Glucagon - Somatostatin

References

  • 1 Poitout V, Rouault C, Guerre-Millo M, Reach G. Does leptin regulate insulin secretion?.  Diabete Metab. 1998;  24 321-326
    PubMedGoogle Scholar
  • 2 Emilsson V, Liu Y -L, Cawthorne M A, Morton N M, 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
    CrossrefPubMedGoogle Scholar
  • 3 Kieffer T, Scott-Heller R, Leech C A, Holz G G, Habener J F. Leptin suppression of insulin secretion by the activation of ATP-sensitive K+ channels in pancreatic beta cells.  Diabetes. 1997;  46 10 087-10 093
    PubMedGoogle Scholar
  • 4 Chen N -G, Swich A G, Romsos D R. Leptin constrains acetylcholine-induced insulin secretion from pancreatic islets of ob/ob mice.  J Clin Invest. 1997;  100 1174-1179
    PubMedGoogle Scholar
  • 5 Fehmann H C, Berghöfer P, Brandhorst D, Bandhorst H, Hering B, Bretzel R G, Göke B. Leptin inhibition of insulin secretion from isolated human islets.  Acta Diabetol. 1997;  34 249-252
    CrossrefPubMedGoogle Scholar
  • 6 Fehmann H C, Bode H P, Ebert T, Karl A, Göke B. Interaction of GLP-1 and leptin at rat pancreatic B-cells: effects on insulin secretion and signal transduction.  Horm Metab Res. 1997;  29 572-576
    PubMedGoogle Scholar
  • 7 Fehmann H -C, Peiser C, Bode H -P. Leptin: A potent inhibitor of insulin secretion.  Peptides. 1997;  18 1267-1273
    CrossrefPubMedGoogle Scholar
  • 8 Pallett A L, Morton N M, Cawthorne M A, Emilsson V. Leptin inhibits insulin secretion and reduces insulin mRNA levels in rat isolated pancreatic islets.  Biochem Biophys Res Commun. 1997;  238 267-270
    CrossrefPubMedGoogle Scholar
  • 9 Ishida K, Murakami T, Mizuno A, Iida M, Kuwajima M, Shima K. Leptin suppresses basal insulin secretion from rat pancreatic islets.  Regul Pept. 1997;  70 179-182
    CrossrefPubMedGoogle Scholar
  • 10 Kulkarni R N, Wang Z -L, Wang R -M, Hurley, Smith D M, Ghatei A, Withers D J, Gardiner J V, Bailey C J, Bloom S R. Leptin rapidly suppresses insulin release from insulinoma cells, rat and human islet and, in vivo, in mice.  J Clin Invest. 1997;  100 2729-2736
    CrossrefPubMedGoogle Scholar
  • 11 Mizuno A, Murakami T, Otani S, Kuwajima M, Shima K. Leptin affects pancreatic endocrine functions through the sympathetic nervous system.  Endocrinology. 1998;  139 3863-3870
    CrossrefPubMedGoogle Scholar
  • 12 Poitout B, Rouault C, Guerre-Mille M, Briaud I, Reach G. Inhibition of insulin secretion by leptin in normal rodent islets of Langerhans.  Endocrinology. 1998;  139 822-826
    CrossrefPubMedGoogle Scholar
  • 13 Ookuma M, Ookuma K, York D A. Effects of leptin on insulin secretion from isolated rat pancreatic islets.  Diabetes. 1998;  47 219-223
    PubMedGoogle Scholar
  • 14 Zhao A z, Bornfeldt K E, Beavo J A. Leptin inhibits insulin secretion by activation of phosphodiesterase 3B.  J Clin Invest. 1998;  102 869-873
    CrossrefPubMedGoogle Scholar
  • 15 Seufert J, Kieffer T J, Leech C A, Holz G G, Moritz W, Ricordi C, Habener J F. Leptin suppression of insulin secretion and gene expression in human pancreatic islets: implications for the development of adipogenic diabetes mellitus.  J Clin Endocrinol Metab. 1999;  84 670-676
    CrossrefPubMedGoogle Scholar
  • 16 Ahrén B, Havel P J. Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line (INS-1 cells).  Am J Physiol. 1999;  277 R959-R966
    PubMedGoogle Scholar
  • 17 Tanizawa Y, Okuya S, Ishihara H, Asano T, Yada T, Oka Y. Direct stimulation of basal insulin secretion by physiological concentrations of leptin in pancreatic beta cells.  Endocrinology. 1997;  138 4513-4516
    CrossrefPubMedGoogle Scholar
  • 18 Shimizu H, Ohtani K -I, Tsuchiya T, Takahasi H, Uehara Y, Sato N, Mori M. Leptin stimulates insulin secretion and synthesis in HIT-T 15 cells.  Peptides. 1997;  18 1263-1266
    CrossrefPubMedGoogle Scholar
  • 19 Leclercq-Meyer V, Considine R V, Sener A, Malaisse W J. Does leptin receptor play a functional role in the endocrine pancreas.  Biochem Biophys Res Commun. 1996;  239 794-798
    PubMedGoogle Scholar
  • 20 Leclercq-Meyer V, Malaisse W J. Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentrations.  Moll Cell Endocrinol. 1998;  25 111-118
    PubMedGoogle Scholar
  • 21 Samson W K, Murphy T C, Robison D, Vargas T, Tau E, Chang J -K. A 35 amino acid fragment of leptin inhibits feeding in the rat.  Endocrinology. 1996;  137 5182-5185
    CrossrefPubMedGoogle Scholar
  • 22 Leclercq-Meyer V, Marchand J, Leclercq R, Malaisse W J. Glucagon and insulin release by the in vitro perfused rat pancreas.  Diabete Metab. 1976;  2 57-65
    PubMedGoogle Scholar
  • 23 Silvestre R A, Miralles P, Moreno P, Villanueva M L, Marco J. Somatostatin, insulin and glucagon secretion by the perfused rat pancreas from cysteamine-treated rats.  Biochem Biophys Res Commun. 186;  134 1291-1297
    PubMedGoogle Scholar
  • 24 Herbert V, Lau K S, Gottlieb C W, Bleicher S J. Coated charcoal immunoassay of insulin.  J Clin Endocrinol Metab. 1965;  25 1375-1384
    CrossrefPubMedGoogle Scholar
  • 25 Faloona G R, Unger R. Glucagon. In: Jaffe BM, Behrman HR (eds). Methods of Hormone Radioimmunoassay.  New York:; Academic Press, 1974: 317-330
    Google Scholar
  • 26 Harris V, Conlon J M, Srikant C B, McCorkle K, Schusdziarra V, Ipp E, Unger R H. Measurement of somatostatin-like immunoreactivity in plasma.  Clin Chim Acta. 1978;  87 275-283
    CrossrefPubMedGoogle Scholar
  • 27 Huang X F, Lin S, Zhang R. Upregulation of leptin receptor mRNA expression in obese mouse brain.  Neuroreport. 1997;  8 1035-1038
    PubMedGoogle Scholar
  • 28 Zawalich W S. Regulation of insulin secretion by phosphoinositide-specific phospholipase C and protein kinase C activation.  Diabetes Rev. 1996;  4 160-176
    PubMedGoogle Scholar
  • 29 Persaud S, Jones J, Sugden P M, Howell S l. The role of protein kinase C in cholinergic stimulation of insulin secretion from rat islets of Langerhans.  Biochem J. 1989;  264 753-758
    PubMedGoogle Scholar
  • 30 Rodríguez-Gallardo J, Silvestre R A, Marco J. Inhibitory effect of enterostatin on the beta cell response to digestive insulinotropic peptides.  Int J Obes. 1999;  23 787-792
    CrossrefPubMedGoogle Scholar
  • 31 Vara E, Fernández-Martin O, García C, Tamarit-Rodríguez J. Palmitate dependence of insulin secretion, “de novo” phospholipid synthesis and 45Ca2+ -turnover in glucose stimulated rat islets.  Diabetologia. 1998;  31 687-693
    PubMedGoogle Scholar
  • 32 Karonen S -L, Koistinen H A, Nikkinen P, Koivisto V A. Is brain uptake of leptin in vivo saturable and reduced by fasting?.  Eur J Nucl Med. 1998;  25 607-612
    CrossrefPubMedGoogle Scholar
  • 33 Scarpace P J, Matheny M, Moore R L, Tümer N. Impaired leptin responsiveness in aged rats.  Diabetes. 2000;  49 431-435
    PubMedGoogle Scholar
  • 34 Cohen S L, Halaas J L, Friedman J M, Chait B T, Bennett L, Chang D, Hecht R, Collins F. Human leptin characterization.  Nature. 1996;  382 589
    PubMedGoogle Scholar

J. Marco

Clínica Puerta de Hierro
Universidad Autónoma de Madrid

San Martín de Porres 4
28035 Madrid
Spain


Fax: Fax:+ 34 (91) 3167667

Phone: Phone:+ 34 (91) 3162240 Ext. 5463

Email: e-mail:jmarco@hpth.insalud.es

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