Leptin: a potent inhibitor of insulin secretion.
The hormone leptin is expressed and secreted by the adipose tissue and impacts on the central nervous system. Leptin is involved in the regulation of energy balance, satiety, and body composition. The lack of active leptin results in obesity, high food intake, hyperglycemia, and hyperinsulinemia. We present data supporting effects of leptin on the endocrine pancreas. We found the leptin receptor to be expressed in insulin- and glucagon-secretin cells derived from mouse, hamster, and rat pancreas. In the isolated perfused rat pancreas leptin is a potent inhibitor of basal and glucose-induced insulin secretion, especially during the first phase of the insulin response. At isolated mouse islets and insulin-secreting INS-1 cells leptin reduced promptly and persistently the intracellular Ca2+ levels. Cytoplasmic Ca2+ oscillation amplitude was decreased and the oscillation frequency increased. These findings suggest functional active receptors for leptin on insulin-secreting B-cells. Therefore, leptin is a metabolic hormone and not only a signal to the brain indicating filled fat stores. Our data suggest that leptin is also a signal back to the endocrine pancreas that no more insulin is required to replenish fat stores. Thus, an "adipo-insular axis" operating with two arms exists: insulin and glucagon are signals to the adipocyte. This releases leptin, which could be the mediator of the respective feedback to the pancreas. A defective leptin suppression of insulin secretion could contribute to hyperinsulinemia and disturbances of glucose metabolism.
Fehmann
H C
HC
Department of Medicine, Philipps-University of Marburg, Germany.
Peiser
C
C
Bode
H P
HP
Stamm
M
M
Staats
P
P
Hedetoft
C
C
Lang
R E
RE
Göke
B
B
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured; D006224:Cricetinae; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007329:Insulin Antagonists / Q000494:pharmacology; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D020738:Leptin; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008811:Mice, Inbred DBA; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007328:Insulin; D007329:Insulin Antagonists; D020738:Leptin; D011506:Proteins; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; D011994:Recombinant Proteins; C515447:leptin receptor, mouse; D012313:RNA; D005934:Glucagon; D002118:Calcium