Dual action of beta-endorphin on insulin release in genetically obese and lean mice.
Intraperitoneal administration of beta-endorphin (1 mg/kg) to ob/ob mice doubled fasting plasma insulin concentrations within 30 min, while plasma glucose concentrations were unaltered. In lean mice, beta-endorphin failed to alter plasma insulin or glucose responses. In glucose-loaded ob/ob mice, beta-endorphin (1 mg/kg) reduced insulin levels at 40 min, and delayed glucose disposal. A lower dose of beta-endorphin (0.1 mg/kg) decreased plasma insulin at 90 min, with no effect on plasma glucose disposal. In lean mice, only the higher dose of beta-endorphin suppressed the glucose-stimulated rise in plasma insulin concentrations, without affecting plasma glucose. Beta-endorphin's actions were blocked by naltrexone and could not be mimicked by N-acetyl-beta-endorphin. Beta-endorphin (10(-8)M) enhanced insulin release from isolated ob/ob and lean mouse islets incubated in medium containing 6 mM glucose, but inhibited release when 20 mM glucose was present. These effects were naloxone reversible. The results indicate that 1) ob/ob mice display a greater magnitude of response in vivo to beta-endorphin's actions on insulin release compared with lean mice, 2) high concentrations of beta-endorphin exacerbate glucose disposal in ob/ob mice. 3) the prevailing glucose concentration is an important determinant of whether beta-endorphin's effects on insulin release will be stimulatory or inhibitory and 4) these actions are mediated via opiate receptors.
Khawaja
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XZ
School of Biological Sciences, University of Sussex, Brighton, England.
Green
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IC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D001615:beta-Endorphin / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D001615:beta-Endorphin; D005947:Glucose