Comparison of antihyperglycemic effects of creatine and glibenclamide in type II diabetic patients.

This study compares the effects of glibenclamide and creatine in type II diabetics. In a 14-day symmetrically randomized crossover trial recently detected type II diabetics received either creatine (3 g) or glibenclamide (3.5 mg) for five successive days, followed by two days of washout, and crossover to the opposite treatment. Glucose, insulin, c-peptide, and creatine were measured. Creatine and glibenclamide decreased glucose concentrations vs. basal glucose [-15, 60, 90, 120, 180, and 240 min; mol/l]: 12.6±0.83 vs. 12.2±0.56 vs. 12.1±0.57, 15.3±0.63 vs. 13.5± 0.70(a ) vs. 13.0±0.57(a), 14.8±0.57 vs. 13.8±0.59(a) vs. 13.4±0.46(a), 14.6±0.61 vs. 12.3±0.49(b) vs. 12.4±0.61(a), 12.8±0.76 vs. 10.0± 0.40(c) vs. 10.3±0.41(c), and 11.4±0.67 vs. 8.3±0.40(c) vs. 8.5±0.36(c); ((a) p<0.05; (b) p<0.01; (c) p<0.001 vs. basal glucose). Treatment with both creatine and glibenclamide increased insulin and c-peptide concentrations after 120 and 240 min (p<0.05 and p<0.01). At the doses applied short-term treatment with creatine and glibenclamide elicits similar glucose lowering effects.

Uric acid may inhibit glucose-induced insulin secretion via binding to an essential arginine residue in rat pancreatic beta-cells.

Uric acid (1a) suppresses basal insulin release in isolated rat pancreatic islets and inhibition of glucose-stimulated insulin secretion (GSIS) occurs right at hyperuricaemic levels (0.4 mM). Conversely, 1 mM guanidinium urate (2a) was completely ineffective, strongly suggesting that binding to an essential arginine residue triggers the inhibitory effect. A specific recognition of 1a molecule at the crucial beta-cell receptor is probably involved in the blocking glucose signal transduction.

Enkephalin degradating enzymes in pheochromocytoma patients.

Adrenal gland as a major source of enkephalins on the periphery can be affected by a rare adrenal gland tumor, adrenal pheochromocytoma. It has been demonstrated that this tumor might be associated with altered concentration of enkephalin-like peptides. The effect of these peptides can be either prolonged or abbreviated by two neutrophil membrane bound enzymes; aminopeptidase N (APN) and neutral endopeptidase (NEP). We assumed that altered enkephalin level in pheochromocytoma patients (but not in patients with non-functional adenomas or tumors of different origin) might result in differently regulated APN and/or NEP activity. We measured APN and NEP activity on surface of neutrophils, level of lipid peroxidation (LPO) in plasma and enkephalin concentration in plasma in patients with pheochromocytomas, non-functional adenomas, malignant renal tumors and healthy controls. Catheholamines and vanyllmandelic acid (VMA) were measured in 24-h urine of pheochromocytoma patients. NEP and APN activity on neutrophils from all pheochromocytoma patients was significantly increased as compared with healthy controls, non-functional adenomas and malignant renal tumors. In all pheochromocytoma patients NEP activity was reduced almost to the control level after surgery. At the same time APN activity was in some patients up- and in others down-regulated. In comparison, elevated levels of cateholamines and VMA were found after multiple determinations in 6 out of 10 pheochromocytoma patients. Although preliminary, this study has shown specifically and consistently up-regulated NEP activity on neutrophils from pheochromocytoma patients, and uniformly decreased NEP activity in these patients after adrenalectomy.