Leptin administration normalizes insulin secretion from islets of Lep(ob)/Lep(ob) mice by food intake-dependent and -independent mechanisms.
Leptin-deficient Lep(ob)/Lep(ob) mice exhibit elevations in plasma insulin early in development. The present study tested the hypothesis that absence of leptin during neonatal development permanently programs islets from these mice to hypersecrete insulin. Administration of leptin for 8 days to young adult Lep(ob)/Lep(ob) mice normalized their food intake, plasma insulin concentration, and insulin secretion in response to glucose, acetylcholine, and leptin. Restriction of food intake per se of Lep(ob)/Lep(ob) mice lowered, but did not normalize, plasma insulin concentrations. Food-restricted Lep(ob)/Lep(ob) mice continued to hypersecrete insulin in response to glucose, but islets from these mice did not hyperrespond to acetylcholine or respond to leptin as occurs in ad libitum-fed Lep(ob)/Lep(ob) mice. We conclude that neonatal leptin deficiency does not permanently program islets from mice to hypersecrete insulin. The hyperphagia associated with leptin deficiency contributes substantially to the hypersecretion of insulin, but leptin also appears to have more direct effects on regulation of insulin secretion.
Lee
Joo-Won
JW
Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824-1224, USA.
Romsos
Dale R
DR
D000109:Acetylcholine / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D001835:Body Weight; D002478:Cells, Cultured; D004032:Diet; D004435:Eating; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D020738:Leptin / Q000008:administration & dosage* / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D007328:Insulin; D020738:Leptin; D005947:Glucose; D000109:Acetylcholine; D000077191:Wortmannin