Somatostatin infusion lowers plasma ghrelin without reducing appetite in adults with Prader-Willi syndrome.
Prader-Willi syndrome (PWS) is characterized by life-threatening childhood-onset hyperphagia, obesity and, uniquely, high plasma levels of ghrelin, the orexigenic gastric hormone. Somatostatin suppresses ghrelin secretion in normal subjects. We therefore examined the effect of somatostatin on plasma ghrelin and appetite in four male PWS adults fasted overnight in a double-blind, placebo-controlled, randomized cross-over study. Subjects received an intravenous infusion of somatostatin (250 microg/hr) or saline for 300 min, and had blood samples taken every 30 min for measurement of plasma ghrelin and PYY3-36 (anorexigenic intestinal hormone) by radio-immunoassay, and glucose. Appetite was measured by counting sandwiches eaten over a 60 min free food access period from +120 min. Despite somatostatin lowering fasting plasma ghrelin by 60 +/- 2% (P = 0.04) to levels seen in non-PWS men, there was no associated reduction in food intake (105 +/- 9% of food intake during saline infusion, P = 0.6). Somatostatin also lowered plasma PYY levels by 45 +/- 16% (P = 0.04), and produced post-prandial hyperglycemia (P = 0.04). We conclude that either hyperghrelinemia may not contribute to hyperphagia in PWS adults, or perhaps concomitant reductions in anorexigenic gastrointestinal hormones by somatostatin counteracted any anorexigenic effect of lowering orexigenic ghrelin. Somatostatin analogues may therefore not be an effective therapy for obesity in PWS. Larger chronic studies with long-acting somatostatin analogues will be needed to determine their benefits and risks in treating PWS obesity.
Tan
Tricia M-M
TM
Department of Endocrinology, Royal Free and University College Hospital Medical School, Royal Free Hospital, Hampstead, London NW3 2QG, United Kingdom.
Vanderpump
Mark
M
Khoo
Bernard
B
Patterson
Mike
M
Ghatei
Mohammad A
MA
Goldstone
Anthony P
AP
D000328:Adult; D001066:Appetite / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004435:Eating / Q000187:drug effects; D054439:Ghrelin; D006728:Hormones / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007262:Infusions, Intravenous; D008297:Male; D010446:Peptide Fragments; D036361:Peptide Hormones / Q000097:blood*; D019894:Peptide YY / Q000097:blood; D019518:Postprandial Period; D011218:Prader-Willi Syndrome / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D013004:Somatostatin / Q000008:administration & dosage* / Q000009:adverse effects
D001786:Blood Glucose; D054439:Ghrelin; D006728:Hormones; D010446:Peptide Fragments; D036361:Peptide Hormones; D019894:Peptide YY; C061785:peptide YY (3-36); D013004:Somatostatin