The Journal of clinical endocrinology and metabolism · 2010
Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans?
СтатьяРандомизированное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Asmar Meena, Bache Michael, Knop Filip K, Madsbad Sten, Holst Jens J
Аннотация
OBJECTIVE: Amylin, cosecreted with insulin, has like glucagon-like peptide-1 (GLP-1) been reported to inhibit glucagon secretion, delay gastric emptying, and reduce appetite and food intake. We investigated whether the effects of GLP-1 on gastric emptying, appetite, and food intake are mediated directly or indirectly via release of amylin.
DESIGN: Eleven C-peptide and amylin-negative patients with type 1 diabetes mellitus (T1DM) and 12 matched healthy controls participated in a placebo-controlled, randomized, single-blinded, crossover study. With glucose clamped between 6 and 9 mm, near-physiological infusions of GLP-1, human amylin, pramlintide, or saline were given for 270 min during and after a fixed meal. Gastric emptying was measured using paracetamol, appetite using visual analog scales, and food intake during a subsequent ad libitum meal (at 240 min).
RESULTS: In T1DM, gastric emptying, food intake, and appetite were reduced equally during low GLP-1 and amylin infusion compared with the saline infusion (P < 0.05). The controls showed stronger suppression of gastric emptying (P < 0.0001) and food intake (P < 0.01) with GLP-1 compared to amylin. Postprandial glucagon responses were reduced in controls and T1DM during GLP-1 and amylin infusions (P < 0.05). Amylin and pramlintide infusion had similar effects.
CONCLUSIONS: GLP-1 exerts its effect on gastric emptying, appetite, food intake, and glucagon secretion directly, although secretion of amylin may contribute to some of these effects in healthy control subjects.
DESIGN: Eleven C-peptide and amylin-negative patients with type 1 diabetes mellitus (T1DM) and 12 matched healthy controls participated in a placebo-controlled, randomized, single-blinded, crossover study. With glucose clamped between 6 and 9 mm, near-physiological infusions of GLP-1, human amylin, pramlintide, or saline were given for 270 min during and after a fixed meal. Gastric emptying was measured using paracetamol, appetite using visual analog scales, and food intake during a subsequent ad libitum meal (at 240 min).
RESULTS: In T1DM, gastric emptying, food intake, and appetite were reduced equally during low GLP-1 and amylin infusion compared with the saline infusion (P < 0.05). The controls showed stronger suppression of gastric emptying (P < 0.0001) and food intake (P < 0.01) with GLP-1 compared to amylin. Postprandial glucagon responses were reduced in controls and T1DM during GLP-1 and amylin infusions (P < 0.05). Amylin and pramlintide infusion had similar effects.
CONCLUSIONS: GLP-1 exerts its effect on gastric emptying, appetite, food intake, and glucagon secretion directly, although secretion of amylin may contribute to some of these effects in healthy control subjects.