title: Glutamate decarboxylase autoimmunity and growth hormone secretion in type I diabetes mellitus.
abstract: Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
authors.affiliation: Department of Internal Medicine and Chemistry, University of Brescia, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Giustina
authors.forename: P
authors.initials: P
authors.lastname: Desenzani
authors.forename: P
authors.initials: P
authors.lastname: Perini
authors.forename: E
authors.initials: E
authors.lastname: Bazzigaluppi
authors.forename: C
authors.initials: C
authors.lastname: Bodini
authors.forename: S
authors.initials: S
authors.lastname: Bossoni
authors.forename: C
authors.initials: C
authors.lastname: Poiesi
authors.forename: W B
authors.initials: WB
authors.lastname: Wehrenberg
authors.forename: E
authors.initials: E
authors.lastname: Bosi
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000150:complications*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D007987:Gonadotropin-Releasing Hormone / Q000097:blood; D019382:Human Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male
chemical_list: D001323:Autoantibodies; D019382:Human Growth Hormone; D007987:Gonadotropin-Releasing Hormone; D005968:Glutamate Decarboxylase