Horm Metab Res 2003; 35(2): 81-85
DOI: 10.1055/s-2003-39055
Original Basic
© Georg Thieme Verlag Stuttgart · New York

Leptin Fully Suppresses Acetylcholine-Induced Insulin Secretion and is Reversed by Tolbutamide in Isolated Perfused Chicken Pancreas

Y.  Benomar1 , N.  Rideau1 , S.  Crochet1 , M.  Derouet1 , M.  Taouis1
  • 1Station de Recherches Avicoles, INRA, F37380 Nouzilly
Further Information

Publication History

Received 24 April 2002

Accepted after revision 28 August 2002

Publication Date:
07 May 2003 (online)

Abstract

So far, there has been no evidence for any direct pancreatic effect of leptin in the chicken. The present study was aimed at detecting chicken leptin receptor (cOb-R) expression in isolated chicken islets of Langerhans and to examine the direct effect of leptin on insulin secretion after stimulation by acetylcholine (1 µM) + glucose (14 mM) from isolated perfused chicken pancreas. We will show that i) full length cOb-R mRNA was expressed in isolated pancreatic islets of chickens, ii) recombinant chicken leptin (10 nM) or diazoxide (100 µM) rapidly (within 2 min) and significantly suppressed insulin secretion induced by acetylcholine stimulation without any change in volume outflow rate, iii) tolbutamide (100 µM) introduced 10 min after leptin and perfused for 10 min fully reversed the suppressive effect of leptin on pre-established acetylcholine-induced insulin release. In conclusion, we found that leptin has a profound inhibitory influence upon insulin secretion in perfused chicken pancreas. The results suggest that leptin inhibits insulin secretion by acting before or at the level of KATP channels in chicken pancreatic β-cells. Further studies are warranted to clarify the specific inhibitory mechanism.

References

  • 1 Campfield L A, Smith F J, Burn P. The OB protein (leptin) pathway - a link between adipose tissue mass and central neural networks.  Horm Metab Res. 1996;  28 619-632
  • 2 Tartaglia L A, Dembski M, Weng X, Deng N, Culpepper J, Devos R, Richards G J, Campfield L A, Clark F T, Deeds J. et al . Identification and expression cloning of a leptin receptor, OB-R.  Cell. 1995;  83 1263-1271
  • 3 Fei H, Okano H J, Li C, Lee G H, Zhao C, Darnell R, Friedman J M. Anatomic localization of alternatively spliced leptin receptors (Ob-R) in mouse brain and other tissues.  Proc Natl Acad Sci U S A. 1997;  94 7001-7005
  • 4 Kieffer T J, Heller R S, Habener J F. Leptin receptors expressed on pancreatic beta-cells.  Biochem Biophys Res Commun. 1996;  224 522-527
  • 5 Kieffer T J, Habener J F. The adipoinsular axis: effects of leptin on pancreatic beta-cells.  Am J Physiol Endocrinol Metab. 2000;  278 E1-E14
  • 6 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: implication for the development of adipogenic diabetes mellitus.  J Clin Endocrinol Metab. 1999;  84 670-676
  • 7 Seufert J, Kieffer T J, Habeher J F. Leptin inhibits insulin gene transcription and reverses hyperinsulinemia in leptin-deficient ob/ob mice. Proc Natl.  Acad Sci. 1999;  96 674-679
  • 8 Taouis M, Chen J W, Daviaud C, Dupont J, Derouet M, Simon J. Cloning the chicken leptin gene.  Gene. 1998;  208 239-242
  • 9 Raver N, Taouis M, Dridi S, Derouet M, Simon J, Robinzon B, Djiane J, Gertler A. Large-scale preparation of biologically active recombinant chicken obese protein (leptin).  Protein Expr Purif. 1998;  14 403-408
  • 10 Ohkubo T, Tanaka M, Nakashima K. Structure and tissue distribution of chicken leptin receptor (cOb-R) mRNA.  Biochim Biophys Acta. 2000;  1491 303-308
  • 11 Denbow D M, Meade S, Robertson A, McMurtry J P, Richards M, Ashwell C. Leptin-induced decrease in food intake in chickens.  Physiology and behavior. 2000;  69 359-362
  • 12 Rideau N, Simon J, Leclercq B. Further characterization of insulin secretion from the perfused duodenum-pancreas of chicken: a comparison of insulin release in chickens selected for high and low abdominal fat content.  Endocrinology. 1986;  119 2635-2641
  • 13 Ruffier L, Simon J, Rideau N. Isolation of functional glucagon islets of Langerhans from the chicken pancreas.  Gen Comp Endocrinol. 1998;  112 153-162
  • 14 Taouis M, Dupont J, Gillet A, Derouet M, Simon J. Insulin receptor substrate 1 antisense expression in an hepatoma cell line reduces cell proliferation and induces overexpression of the src homology 2 domain and collagen protein (SHC).  Molecular and cellular endocrinology. 1998;  137 177-186
  • 15 Simon J, Derouet M, Gespach C. An anti-insulin serum, but not a glucagon antagonist, alters glycemia in fed chickens.  Horm Metab Res. 2000;  32 139-141
  • 16 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
  • 17 Kieffer T J, Heller R S, 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 1087-1093
  • 18 Horev G, Einat P, Aharoni T, Eshdat Y, Friedman-Einat M. Molecular cloning and properties of the chicken leptin-receptor (CLEPR) gene.  Mol Cell Endocrinol. 2000;  162 95-106
  • 19 Rideau N. Peculiarities of insulin secretion in chickens.  Ann N Y Acad Sci. 1998;  839 162-165
  • 20 Chen N G, Swick 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
  • 21 Silvestre R A, Rodriguez-Gallardo J, Egido E M, Marco J. Effect of leptin on insulin, glucagon, and somatostatin secretion in the perfused rat pancreas.  Horm Metab Res. 2001;  33 207-212
  • 22 Harvey J, McKenna F, Herson P S, Spanswick D, Ashford M L. Leptin activates ATP-sensitive potassium channels in the rat insulin-secreting cell line, CRI-G1.  J Physiol (Lond). 1997;  504 527-535
  • 23 Rideau N. Insulin secretion in birds, Leanness in domestic birds. Genetic, metabolic, and hormonal aspects. Tours, 4 - 6/08/1987. Butterworths (GBR) 1987: p. 269-294
  • 24 Samols E, Tyler J, Marks V. Glucagon-insulin interrelationships. Glucagon Molecular Physiology. In: Clinical and Therapeutic Implications Lefebvre J, Unger R (eds) Oxford; Pergamon Press 1972: 151 ff
  • 25 Rideau N. Insulin secretion. In: Harvey S, Etches RJ (eds). Perspectives in Avian Endocrinology Bristol; Journal of endocrinology Ltd 1997: 329-334

N. Rideau

Station de Recherches Avicoles, INRA

F37380 Nouzilly · France

Phone: + 33 (42) 47 79 40

Fax: + 33 (42) 47 77 78

Email: rideau@tours.inra.fr