Postprandial total ghrelin suppression is modulated by melanocortin signaling in humans.

Contents: Ghrelin is implicated in meal initiation because circulating levels increase before and fall after meal consumption. In rodents, ghrelin stimulates food intake via hypothalamic circuits expressing the melanocortin 4 receptor (MC4R).

Objective: The aim of the study was to investigate the impact of central melanocortinergic tone on ghrelin secretion in humans.

Obesity due to melanocortin 4 receptor (MC4R) deficiency is associated with increased linear growth and final height, fasting hyperinsulinemia, and incompletely suppressed growth hormone secretion.

Context: Melanocortin receptor 4 (MC4R) deficiency is characterized by increased linear growth greater than expected for the degree of obesity.

Objective: The objective of the investigation was to study the somatotroph axis in obese MC4R-deficient patients and equally obese controls.

Patients And Methods: We obtained anthropometric measurements and insulin concentrations in 153 MC4R-deficient subjects and 1392 controls matched for age and severity of obesity.

Oral glutamine increases circulating glucagon-like peptide 1, glucagon, and insulin concentrations in lean, obese, and type 2 diabetic subjects.

Background: Incretin hormones, such as glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), play an important role in meal-related insulin secretion. We previously demonstrated that glutamine is a potent stimulus of GLP-1 secretion in vitro.

Objective: Our objective was to determine whether glutamine increases circulating GLP-1 and GIP concentrations in vivo and, if so, whether this is associated with an increase in plasma insulin.

A POMC variant implicates beta-melanocyte-stimulating hormone in the control of human energy balance.

The melanocortin-4 receptor (MC4R) plays a critical role in the control of energy balance. Of its two pro-opiomelanocortin (POMC)-derived ligands, alpha- and beta-MSH, the majority of attention has focused on alpha-MSH, partly reflecting the absence of beta-MSH in rodents. We screened the POMC gene in 538 patients with severe, early-onset obesity and identified five unrelated probands who were heterozygous for a rare missense variant in the region encoding beta-MSH, Tyr221Cys.