Leptin receptors expressed on pancreatic beta-cells.
Leptin (Ob protein) is a recently isolated hormone produced by adipocytes and is a powerful regulator of satiety centers in the brain. A defect in either leptin production or transmission of the leptin signal in animal models, i.e. ob/ob and db/db mice, respectively, results in a syndrome of obesity and diabetes which closely resembles that which occurs in humans. Leptin release is regulated in part by nutritional status and its expression in adipose tissue is up-regulated by insulin. Since hyperinsulinemia is a primary defect in ob/ob and db/db mice which manifests early in the disease, we postulated that leptin may also regulate insulin release as part of a "adipoinsular' feedback loop. We demonstrate the expression of leptin receptor mRNA in primary rat pancreatic islets and in the insulinoma cell line beta TC-3. Furthermore, we find binding of 125I-leptin to beta TC-3 cells which is significantly displaced by leptin. These findings suggest the possibility that the binding of leptin to its receptor in beta-cells may modulate insulin expression in a negative feedback loop, and thereby may have an anti-obesity effect.
Kieffer
T J
TJ
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard Medical School, Boston 02114, USA.
Heller
R S
RS
Habener
J F
JF
D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D017931:DNA Primers; D003920:Diabetes Mellitus / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D007515:Islets of Langerhans / Q000378:metabolism*; D007700:Kinetics; D020738:Leptin; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008954:Models, Biological; D008969:Molecular Sequence Data; D009765:Obesity; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin
D002352:Carrier Proteins; D017931:DNA Primers; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C515447:leptin receptor, mouse