Cholinergic muscarinic receptor blockade suppresses arginine- and exercise-induced growth hormone secretion in type I diabetic subjects.
Stimulatory cholinergic pathways participate in the regulation of GH release, and cholinergic receptor antagonists inhibit GH secretion in normal man. Whether similar mechanisms are active in subjects with insulin-dependent diabetes is not known, yet this is of potential importance since GH hypersecretion has been implicated in both the acute and chronic complications of diabetes mellitus. To address this question we studied the effects of cholinergic receptor blockade on stimulated GH release in 18 type I diabetic men. Paired tests were performed using 1 of 2 different stimuli (30 g arginine, iv, or physical exercise for 30 min) with or without prior administration of the selective cholinergic muscarinic receptor antagonist pirenzepine (30 mg, iv). Arginine elicited a mean peak serum GH level of 9.0 +/- 1.9 (+/- SEM) micrograms/L, which was completely suppressed by pirenzepine (1.5 +/- 0.4 micrograms/L; n = 8; P less than 0.01). Blood glucose rose after arginine infusion and was not affected by pirenzepine. Serum GH levels rose during physical exercise to a mean peak of 7.3 +/- 1.6 micrograms/L, which was abolished by pirenzepine (1.2 +/- 0.3 micrograms/L; n = 10; P less than 0.01). Blood glucose was not influenced by pirenzepine. Two subjects had no serum GH response to exercise. We conclude that GH secretion in subjects with insulin-dependent diabetes, as in normal subjects, is modulated by cholinergic pathways and is responsive to pharmacological suppression by muscarinic receptor blockade. This may have implications for therapeutic trials designed to lower elevated GH levels in subjects with diabetes mellitus.
Arends
J
J
Fachklinik für Diabetes und Stoffwechselkrankheiten, Bad Lauterberg im Harz, West Germany.
Wagner
M L
ML
Willms
B L
BL
D000328:Adult; D001120:Arginine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology; D013006:Growth Hormone / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion; D010890:Pirenzepine / Q000494:pharmacology; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013546:Sweating / Q000187:drug effects
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D013006:Growth Hormone; D001120:Arginine