The diabetogenic effect of prolactin observed in patients with pathological hyperprolactinaemia was verified in healthy subjects. Plasma prolactin elevation was induced by administration of a dopamine antagonist drug domperidone (Motilium 10 mg orally, 9 subjects) and 2 h later the oral glucose tolerance test was performed. The influence of dopamine receptor stimulation on glucose homeostasis was tested by dopamine infusion (0.3 mg in saline or 20 % glucose, 1 g/min for 60 min, 11 subjects). After the blockade of dopamine receptors, a significant and prolonged increase of prolactin concentration was found. However, the levels of glucose, insulin, and C- peptide either before or after the glucose load were not different from control ones. The decreased number of insulin receptors (1.97±0.41 vs 0.51 ±0.14 pmol per 2.109 red blood cells) was compensated by increased affinity (0.51 ±0.17 vs 1.00±0.22 K* 108 mol.-1 per 1]) of insulin receptors. The stimulation of dopamine receptors showed a negligible effect on glucose regulation. It may be suggested that an endogenous increase of prolactin concentration in the physiological range does not participate in the regulation of glucose homeostasis in healthy subjects.
Current knowledge suggests a complex role of C-peptide in human physiology, but its mechanism of action is only partially understood. The effects of C-peptide appear to be variable depending on the target tissue, physiological environment, its combination with other bioactive molecules such as insulin, or depending on its concentration. It is apparent that C-peptide has therapeutic potential for the treatment of vascular and nervous damage caused by type 1 or late type 2 diabetes mellitus. The question remains whether the effect is mediated by the receptor, the existence of which is still uncertain, or whether an alternative non-receptor-mediated mechanism is responsible. The Institute of Endocrinology in Prague has been paying much attention to the issue of C-peptide and its metabolic effect since the 1980s. The RIA methodology of human C-peptide determination was introduced here and transferred to commercial production. By long-term monitoring of C-peptide oGTT-derived indices, the Institute has contributed to elucidating the pathophysiology of glucose tolerance disorders. This review summarizes the current knowledge of C-peptide physiology and highlights the contributions of the Institute of Endocrinology to this issue., Daniela Vejrazkova, Marketa Vankova, Petra Lukasova, Josef Vcelak, Bela Bendlova., and Obsahuje bibliografii
Our study compared total C-peptide secretion after administration of whey proteins and whey proteins in combination with glucose with results of classical tests assessing beta cell function in the pancreas of healthy individuals. Eight young, healthy (7 males, 1 female; aged 20-26 years), nonobese (BMI: 17-25.9 kg/m2 ) participants with normal glucose tolerance underwent six C-peptide secretion tests. Three secretion tests measured C-peptide response to orally administered substances: whey proteins only (OWT), whey proteins with glucose (OWGT) and glucose only (OGTT); while three secretion tests measured C-peptide response to intravenously administered substances: arginine (AST), glucagon (GST) and glucose (IVGTT). OWT stimulated a greater (93 %, p<0.05) C-peptide response than AST and a 64 % smaller response (p<0.05) than OGTT. OWT also showed lower variability (p<0.05) in C-peptide responses compared to OWGT and OGTT. The greatest total C-peptide response was induced by OWGT (36 % higher than glucose). OWT consistently increased C-peptide concentrations with lower individual variability, while insignificantly increasing glucose levels. Results of this study suggest that both dietology and beta-cells capacity testing could take advantage of the unique property of whey proteins to induce C-peptide secretion., E. Wildová, ... [et al.]., and Obsahuje seznam literatury
Variability in the number of tandem repeats of the insulin gene (INS VNTR) is probably involved in the genetic regulation of insulin secretion. The aim of this study was to investigate the association of INS VNTR polymorphism with the presence of glutamic acid decarboxylase antibodies (GADA) and C-peptide levels in patients with the onset of diabetes after 35 years of age. We investigated 117 patients, median of age 63 (range 40-83) years, median of diabetes duration 8 (range 1-30) years; 31 GADA-positive and 86 GADA-negative subjects. INS VNTR polymorphism was typed indirectly using – 23HphI (T/A) polymorphism, which is in complete linkage disequilibrium with INS VNTR. The I/I, I/III and III/III genotypes were found in 22 (71 %), 8 (26 %), 1 (3 %) GADA-positive individuals and in 39 (45 %), 35 (41 %), 12 (14 %) GADA-negative individuals, respectively. The Class I allele and the genotype I/I were significantly associated with the presence of GADA (OR=2.72, CI 95 %=1.29-5.73 and OR=2.95, CI 95 %=1.22-7.13). The presence of Class III allele was significantly associated with a higher level of postprandial C-peptide in GADA-positive subjects, even when regarding the duration of diabetes. Our results of INS VNTR polymorphism in patients with the onset of diabetes after 35 years of age confirm the association of Class I INS VNTR with autoimmune diabetes and the protective effect of Class III INS VNTR on the insulin secretion in GADA-positive subjects.