Do the actions of glucagon-like peptide-1 on gastric emptying, appetite, and food intake involve release of amylin in humans?
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.


METHODS
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.
Asmar
Meena
M
Department of Endocrinology, Hvidovre Hospital, DK-2650 Hvidovre, Denmark.
Bache
Michael
M
Knop
Filip K
FK
Madsbad
Sten
S
Holst
Jens J
JJ
D000328:Adult; D000682:Amyloid / Q000097:blood / Q000378:metabolism* / Q000494:pharmacology; D001066:Appetite / Q000187:drug effects* / Q000502:physiology; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D005746:Gastric Emptying / Q000187:drug effects* / Q000502:physiology; D005934:Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D058228:Islet Amyloid Polypeptide; D012016:Reference Values; D016037:Single-Blind Method
D000682:Amyloid; D002096:C-Peptide; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D058228:Islet Amyloid Polypeptide; C105254:pramlintide