EFFECTS OF CHOLINERGIC MODULATION ON SERUM INSULIN-LIKE GROWTH FACTOR-L AND ITS BINDING-PROTEINS IN NORMAL AND DIABETIC SUBJECTS

OBJECTIVE We wished to study alterations in serum insulin-like growth factor-I (IGF-I) and its binding proteins in subjects with insulin dep endent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation, In a ddition, we have investigated whether cholinergic modulation exerts an y effects on IGF-I secretion, independently of any actions on GH secre tory status. DESIGN All subjects received GH releasing hormone (GHRH) 1-44; 80 mu g i.v.) alone and 60 minutes following 120 mg of pyridosti gmine orally or 200 mg of pirenzepine orally, The three tests were car ried out in random order at least one week apart. Blood was sampled at 15-minute intervals over 120 minutes. PATIENTS Twelve male subjects w ith IDDM and no clinical evidence of complications were selected on th e basis of HbA(1) levels to provide a wide range of metabolic control, Six normal male subjects were also studied. MEASUREMENTS Serum IGF-I, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA, were m easured before each study to provide measures of metabolic control. RE SULTS Serum IGF-I and IGFBP-3 levels were significantly lower while se rum IGFBP-I levels were significantly higher in the diabetic subjects. Pirenzepine had no effect on serum IGF-I, IGFBP-1 or IGFBP-3 in diabe tic subjects but caused a significant increase in serum IGF-I and IGFB P-3 levels in normal subjects. Pyridostigmine had no effect on IGF-I, IGFBP-1 or IGFBP-3 in either diabetic or normal subjects. IGFBP-1 leve ls were significantly correlated with fasting plasma glucose but no co rrelation was demonstrated between measures of diabetic control and se rum IGF-I or IGFBP-3 levels in diabetic subjects, nor was there any co rrelation between GH responses to GHRH alone or after pirenzepine or p yridostigmine pretreatment and serum levels of IGF-I, IGFBP-1 or IGFBP -3. CONCLUSION These data confirm that subjects with IDDM have reduced serum IGF-I and IGFBP-3 and increased IGFBP-1 levels, the latter bein g directly related to the fasting plasma glucose concentrations, The a bsence of any relation between changes in the IGF-I system and altered GH neuroregulation after cholinergic modulation suggests that changes in IGF-I are not the sole contributors to the altered GH neuroregulat ion which occurs in IDDM. We have also shown an acute stimulatory effe ct of pirenzepine on serum IGF-I and IGFBP-3 in normal subjects which is not present in IDDM although the underlying mechanism is unknown.