title: The impact of insulin-independent, glucagon-induced suppression of total ghrelin on satiety in obesity and type 1 diabetes mellitus.
abstract: OBJECTIVE
  The mechanisms underlying glucagon-induced satiety are incompletely understood. The glucagon-induced reduction in total ghrelin exerted at the hypothalamo-pituitary level might be responsible for this effect. Here we investigated glucagon-suppressive effects on circulating total and acyl-ghrelin, both in obesity and in type 1 diabetes mellitus (T1DM), with respect to the role of glucagon in appetite control. We further aimed to identify a possible mechanistic impact of changes in endogenous insulin.
  
  
  METHODS
  In our prospective, double-blinded, placebo-controlled study, we investigated the endocrine and metabolic responses to intramuscular glucagon administration in 13 patients with T1DM (6 males, 7 females; body mass index [BMI] 24.8 ± 0.95 kg/m(2)), 11 obese participants (OP; 5 males, 6 females; BMI 34.4 ± 1.7 kg/m(2)), and 13 healthy lean participants (LP; 6 males, 7 females; BMI 21.7 ± 0.6 kg/m(2)).
  
  
  RESULTS
  As compared with placebo, glucagon significantly increased satiety index in T1DM and in LP (P < .001) but failed to induce satiety in OP (P = .152). Total ghrelin significantly decreased after glucagon administration in all study groups (P < .01). Similarly, acyl-ghrelin significantly decreased in LP (P < .01). However, acyl-ghrelin concentrations showed no change in OP (P = .248) and even increased substantially in T1DM (P < .01). Changes in acyl-ghrelin correlated positively with changes in nonesterified fatty acid concentrations in all groups (r = 0.31-0.43; P < .01).
  
  
  CONCLUSIONS
  Glucagon-induced satiety was preserved in T1DM but not in obesity. This effect was unrelated to changes in total or acylated ghrelin and was independent of endogenous insulin release. In contrast to the insulin-independent glucagon-induced suppression of total ghrelin, glucagon- and/or insulin-induced modification of lipolysis may determine changes in acylated ghrelin.
authors: MD, Department of Endocrinology, Diabetes, and Nutrition, Charité-University Medicine Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany. ayman.arafat@charite.de.
authors: A M
authors: AM
authors: Arafat
authors: M O
authors: MO
authors: Weickert
authors: A
authors: A
authors: Adamidou
authors: B
authors: B
authors: Otto
authors: F H
authors: FH
authors: Perschel
authors: J
authors: J
authors: Spranger
authors: M
authors: M
authors: Möhlig
authors: A F H
authors: AF
authors: Pfeiffer
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D054439:Ghrelin / Q000097:blood*; D005934:Glucagon / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000503:physiopathology*; D012527:Satiation / Q000187:drug effects*; D012528:Satiety Response / Q000187:drug effects
chemical_list: D054439:Ghrelin; D005934:Glucagon