Obestatin is supposed to be involved in nutrient homeostasis. Therefore, basal plasma obestatin levels were investigated in 321 normal weight and obese subjects in relation to body mass index, gender, age, insulin concentrations, and type 2 diabetes mellitus. Additionally, postprandial obestatin levels were determined in 20 normal weight subjects. Basal obestatin levels in females were higher compared to males (193.6+/-5.8 vs. 140.6+/-5.1 pg/ml). Obestatin levels correlated inversely and significantly with body mass index (f: r=-0.632, p<0.001; m: r=-0.487, p<0.001) and basal insulin levels (f: r=-0.536, p<0.001; m: r=-0.320, p=0.008) in females and males. However, in a multiple regression analysis as well as in a matched comparison of a low and high insulin group no significant relationship between insulin and obestatin levels was observed in nondiabetics. On the other hand, inclusion of type 2 diabetics with higher insulin levels resulted in a significant inverse correlation. Obestatin levels were independent of age in both sexes. In patients with type 2 diabetes mellitus basal obestatin levels were not different compared to nondiabetic subjects when matched for gender, body mass index, and insulin. In normal weight subjects, postprandial obestatin levels showed a significant decrease between 60 and 90 minutes rising to basal levels thereafter. The present data demonstrate a relation of plasma obestatin levels to body weight, gender and food intake, but not to age. The inverse relationship with insulin might depend on the level of hyperinsulinemia. The present data are compatible with a potential role of obestatin in nutrient regulation.
In the present study, the effects of orally administered beta-casomorphins (beta-CM) and met-enkephalin on postprandial plasma somatostatin-like immunoreactivity (SLI) were assessed in conscious dogs. The intragastric instillation of a liver extract-sucrose test meal containing 12 mg beta-CM or 10 mg met-enkephalin, respectively, augmented the postprandial rise of peripheral vein plasma SLI levels significantly. This effect was inhibited by the additional administration of the specific opiate-receptor antagonist, naloxone. When liver extract-sucrose was dissolved in fresh bovine milk the increase of plasma SLI levels was significantly greater than liver extract-sucrose dissolved in water. This milk-induced augmentation of SLI levels was also reduced by naloxone. Since these opiate-active compounds have an influence upon insulin release when given iv, the effect of beta-CM-7, beta-CM-5, beta-CM-4 beta-CM-4-amide, and met-enkephalin on SLI levels was assessed during their iv infusion at a rate of 1 nmol/kg . h during an iv background infusion of a glucose-amino acid mixture. The infusion of beta-CM-5 elicited a stimulation of peripheral vein SLI levels, whereas the infusion of met-enkephalin resulted in a significant decrease of SLI levels. beta-CM-7, beta-CM-4, and beta-CM-4-amide had no effect on plasma SLI levels at the dose employed. The present data demonstrate that in dogs the ingestion of opiate-active peptide stimulates postprandial SLI release, indicating that nutrient-contained opiate-active material (exorphins) might participate in the regulation of postprandial gastrointestinal endocrine function.
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