Does leptin regulate insulin secretion?
The hormone leptin secreted by adipocytes plays a major role in body weight homeostasis. Its main target is the hypothalamus, but it also affects several peripheral tissues directly. The direct effect of leptin on insulin secretion by pancreatic beta cells has been investigated in several studies, though with controversial results. Interpretation of these data must take into account the animal model and the leptin concentrations used. Experiments carried out on islets from ob/ob mice harbouring a mutation in the leptin gene are not representative of the leptin effect in normal animals because ob/ob islets are very sensitive to the hormone and show altered regulation of insulin secretion. In normal rodent islets, physiological concentrations of leptin seem to inhibit insulin secretion only when the islets are maximally stimulated with high concentrations of glucose associated with secretion potentiators. Several isoforms of the leptin receptor are expressed in pancreatic beta cells. Indirect experimental evidence suggests that leptin signalling in islets requires the long isoform of the receptor. The molecular mechanisms underlying the effect of leptin on insulin secretion are unknown. Our hypothesis is that physiological concentrations of leptin in normal rodents do not affect the direct pathway (coupling a rise in glucose concentration to insulin secretion) but modulate a potentiation of glucose-induced insulin secretion involving cyclic AMP or phospholipase C/protein kinase C activation.
Poitout
V
V
Pacific Northwest Research Institute, Seattle, WA 98122, USA. vpoitout@pnrf.org
Rouault
C
C
Guerre-Millo
M
M
Reach
G
G
D017667:Adipocytes / Q000502:physiology; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D005947:Glucose / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin; D051379:Mice; D008820:Mice, Obese; D011506:Proteins / Q000494:pharmacology / Q000502:physiology*
D007328:Insulin; D020738:Leptin; D011506:Proteins; D005947:Glucose