An abnormal growth hormone (GH) increase after non-specific stimuli (such as TRH, LHRH and, in a few cases, metoclopramide), has been described in insulin-dependent diabetes. Sixty-nine non-hypogonadic male insulin-dependent diabetic patients (mean age 38.6 years, range 18-54; mean duration of diabetes 11.1 years, range 1.3-28, in different degree of metabolic control, some of them with retinopathy, nephropathy and peripheral and/or autonomic neuropathy) were tested twice with 10 mg i.v. metoclopramide (MCP), an antidopaminergic agent with weak serotoninergic activity. Anomalous GH response (i.e. GH increment equal to or higher than 5 ng/ml from basal level) occurred in 33 patients (47.8%). Mean (±SE) MCP-induced GH release in these 'responder' patients peaked up to 17.2±1.7 ng/ml in comparison with no variation found in 'non-responders' and in 25 healthy control men. Abnormal GH secretion appeared to be unrelated to age, metabolic control, basal GH values and duration of diabetes. Moreover, it remained unmodified by pretreatments with placebo, cimetidine, meclastine, propranolol, acetylsalicylic acid and naloxone, while it was enhanced by metergoline, significantly reduced by bromocriptine and almost completely blunted by pirenzepine, a cholinergic muscarinic receptor antagonist. Neuropathy and nephropathy were equally distributed in the two groups, while retinopathy was more frequent in 'responders'. In conclusion, the exact mechanism(s) by which MCP may induce a paradoxical GH release in many insulin-dependent diabetic patients, is still unclear; it might be dependent, at least in part, on the activation of cholinergic pathways. Indeed, it seems to indicate the presence, in diabetes, of a rather complex derangement in the regulatory mechanisms of GH secretion.
- Growth hormone
- Insulin-dependent diabetes mellitus
ASJC Scopus subject areas
- Internal Medicine
- Endocrinology, Diabetes and Metabolism