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A F H Pfeiffer

Publications and source records attributed to A F H Pfeiffer.

32 records · Page 2Linked to original sources
PubMed2005

Adaptation of the hypothalamic-pituitary hormones during intensive endurance training.

OBJECTIVE: Physical activity leads to changes in the hypothalamic-pituitary hormonal system. However, acute and long-term adaptations have not yet been precisely characterized. In this study, the changes of the hormonal system as a result of marathon training and running a marathon were examined. In particular, we focused on adaptations of the hypothalamic-pituitary-adrenocortical (HPA) axis, regarding the activation or inactivation of cortisol to cortisone by the 11beta-hydroxysteroid-dehydrogenase system (11beta-HSD). DESIGN: Patient measurements: 8 healthy women and 11 healthy men volunteered for this study. Blood samples, 24-h urine and a dexamethasone suppression test were analysed for metabolic and hormonal parameters at five different dates 12 weeks around a marathon. RESULTS: Cortisol and ACTH values decreased significantly 2 days after the marathon, whereas the activity of the whole body 11beta-HSD-1 was up-regulated. An increased suppression of cortisol levels was observed in the dexamethasone suppression test after 6 weeks of reduced training levels. Ghrelin was elevated 2 days after the marathon. Only minor changes in the other hypothalamic-pituitary-hormonal axes could be observed. However, the free androgen index increased significantly after 6 weeks of reduced training. CONCLUSIONS: The HPA system appeared to become chronically activated by continuous physical training and therefore less sensitive to the dexamethasone suppression test. The acute stress of the marathon led to a central exhaustion of the HPA system with a paracrine counteraction by the activation of the 11beta-HSD system. Changes in the other hypothalamic-pituitary hormonal axes were the result of long-term differences in training levels and were not altered by the marathon.

Adaptation, Physiological↗
PubMed2005

Glucagon inhibits ghrelin secretion in humans.

OBJECTIVE: It is well known that i.m. glucagon administration stimulates GH and cortisol release in humans, although the mechanisms are unclear. These effects are similar to those described for ghrelin on somatotroph and corticotroph function. The aim of the present study was to investigate the role of ghrelin in mediating the stimulatory effects of glucagon and to evaluate the effect of glucagon on ghrelin secretion. DESIGN AND METHODS: We studied the endocrine and metabolic response to i.m. glucagon administration in 24 subjects (14 men, 10 women; age 19-65 years; body mass index, 25.3 +/- 1 kg/m(2)), who were shown to have an intact anterior pituitary function as evaluated before enclosure. RESULTS: Serum ghrelin concentrations fell significantly at 30, 60, 120 and 180 min after glucagon administration (means +/- s.e.m.; baseline, 377.9 +/- 34.5 pg/ml; nadir, 294.6 +/- 28.3 pg/ml (60 min); P < 0.01). Conversely, i.m. glucagon elicited an increase in GH (baseline, 1.5 +/- 0.4 microg/l; peak, 14.2 +/- 2.7 microg/l (180 min); P < 0.01) and cortisol concentrations (baseline, 452.6 +/- 35.2 nmol/l; peak, 622.1 +/- 44 nmol/l (180 min); P < 0.01). The changes in ghrelin concentration at both 120 and 180 min were still significant after correction for glucose and insulin (P < 0.05). CONCLUSIONS: We show that i.m. glucagon decreases ghrelin significantly. Therefore, the already known stimulatory effects of i.m. glucagon on cortisol and GH are not mediated by a change in ghrelin concentrations. The mechanisms underlying the ghrelin suppression after i.m. glucagon are unlikely to include glucose or insulin variations and need to be further elucidated.

Adult↗
PubMed2004

Enhancement of early- and late-phase insulin secretion and insulin sensitivity by the combination of repaglinide and metformin in type 2 diabetes mellitus.

The effects of a combination of repaglinide and metformin on the insulin secretion pattern and insulin sensitivity were studied in a fixed-dose, open-label, placebo-controlled cross-over study. Eleven patients with T2 DM were allocated in random order to treatment with placebo or repaglinide (1 mg pre-meal 3 x/day) in combination with metformin (2550 mg/day) for one-week periods of each. At the end of each period a hyperglycaemic (HC) and a euglycaemic clamp (EC) were performed. Both early (0 - 10 min) and late (25 - 180 min) phases of insulin secretion were significantly increased during HC with repaglinide compared to placebo (263.3 +/- 133.1 vs. 443.6 +/- 138.5 pmol/l/10 min, p = 0.008 and 18 750.9 +/- 5936.4 vs. 34 508.65 +/- 9234.0 pmol/l/25 - 180 min; p = 0.008). The C-peptide concentrations under steady-state conditions were lower in EC with placebo than with repaglinide (p = 0.014). When euglycaemia was achieved in EC, the C-peptide concentrations decreased from hyperglycaemic to normoglycaemic values in the presence of repaglinide but remained higher than after placebo. The insulin sensitivity index (ISI) was increased by 35 % after 1 week of combination therapy with repaglinide plus metformin (1.11 +/- 0.03 x 10 (2) vs. 0.83 +/- 0.21 x 10 (2) mg x kg (-1) body weight x min (-1) x pmol (-1) x l, respectively; p = 0.033). Repaglinide increased early and late phases of insulin responses in HC, without markedly enhancing insulin secretion in euglycaemia. Repaglinide in combination with metformin produced a significant enhancement of ISI, suggesting a synergistic effect on insulin sensitivity.

Adult↗
PubMed2004

Endogenous and exogenous glucocorticoids decrease plasma ghrelin in humans.

OBJECTIVE: The orexigenic and adipogenic peptide hormone ghrelin is predominantly produced and secreted by the stomach and seems to transduce changes in food intake to specific neuronal circuits in the brain. The activity of ghrelin also includes stimulatory effects on the corticotropic system. However, little is known about the influence of glucocorticoids on ghrelin levels. We therefore studied human plasma ghrelin levels in the presence and absence of elevated glucocorticoid levels of either endogenous or exogenous origin. METHODS: Plasma ghrelin levels were measured in five patients with chronic hypercortisolism (aged 29-58, median 46 years) due to Cushing's syndrome before and after successful surgery for the adenoma, and in eight healthy controls (aged 24-39, median 27.5 years) before and after 30 mg prednisolone (for 5 days) once a day in the morning (median body mass index (BMI) 22.7 kg/m(2)). Plasma ghrelin levels were measured with a commercially available radioimmunoassay. RESULTS: In patients with Cushing's syndrome, plasma ghrelin levels were low (median 363.2 pg/ml, range 161.9-525.7 pg/ml) and significantly increased by 26.6% (P=0.04) after successful surgery, while BMI decreased (median 26.2-24.0 kg/m(2), P=0.04). A strong negative correlation (r=-0.9, P=0.04) between changes in BMI and plasma ghrelin was observed. In healthy controls, plasma ghrelin levels (median 288.7 pg/ml, range 119.6-827.8 pg/ml) were significantly suppressed by 18.3% (P=0.04) after prednisolone treatment. CONCLUSIONS: We have shown for the first time that plasma ghrelin levels are decreased under endogenously or exogenously induced hypercortisolism, making ghrelin an unlikely candidate for causing the changes in energy balance or body composition characteristic of Cushing's disease. However, the reduced ghrelin secretion could reflect a compensation mechanism in reaction to the metabolic consequences of chronic hypercortisolism.

Adult↗
PubMed2003

Post-prandial decrease of human plasma ghrelin in the absence of insulin.

Ghrelin is the most powerful orexigenic hormone in mammalian physiology. Ghrelin plasma concentrations increase prior to meal onset, but decrease post-prandially. We and others reported previously that insulin reduces circulating ghrelin levels and might therefore be a driving force for post-prandial suppression of ghrelin. To test the influence of insulin on post-prandial ghrelin regulation, a patient with Type I diabetes with complete insulin deficiency received a low glycemic index meal and subsequently an additional high glycemic index meal in the absence of insulin substitution. Subsequently, a sc injection of 0.08 IU Lispro insulin per kg body weight was given. Results were compared to those of a healthy control subject matched for sex, age and body mass index, which was undergoing the same test series (without Lispro bolus) in the presence of endogenous post-prandial insulin secretion. A substantial decrease of plasma ghrelin levels was observed in the insulin-deficient patient following low glycemic index carbohydrate load (27% plasma ghrelin decrease). The subsequent exposure to a high glycemic index meal resulted in a slight additional reduction of ghrelin levels (32% from baseline), while Lispro bolus did not induce further changes in circulating ghrelin (27% of baseline at termination). This post-prandial response was comparable to that of the healthy control subject (33% reduction after the first meal, 40% after the second meal). These data tentatively suggest that post-prandial secretion of ghrelin is not exclusively regulated by plasma insulin or plasma glucose but may depend on other metabolic factors yet to be identified.

Adult↗
PubMed2003

Ca2+/calmodulin-dependent protein kinase II delta2 regulates gene expression of insulin in INS-1 rat insulinoma cells.

Ca(2+)/calmodulin-dependent protein kinase II is a member of a broad family of ubiquitously expressed Ca(2+) sensing serine/threonine-kinases. Ca(2+)/calmodulin-dependent protein kinase II is highly expressed in insulin secreting cells and is associated with insulin secretory granules and has been proposed to play an important role in exocytosis or in insulin granule transport to release sites. To elucidate its function the antisense sequence of the major beta-cell subtype, Ca(2+)/calmodulin-dependent protein kinase II delta(2), was stably expressed in INS-1 rat insulinoma cells. This caused a loss of Ca(2+)/calmodulin-dependent protein kinase II delta(2) expression at the mRNA and protein level, while the expression of the 95% homologous Ca(2+)/calmodulin-dependent protein kinase II gamma and of beta-cell specific proteins such as the homeodomain factor pancreatic-duodenal homeobox factor-1 (PDX-1, also referred to as islet/duodenum homeobox-1, IDX-1, insulin promoter factor-1, IPF-1 and somatostatin transactivating factor-1, STF-1), the glucagon-like peptide-1 (GLP-1) receptor and K(ATP)-channels K(IR)6.2/SUR-1 (sulfonylurea receptor-1) was not altered. Unexpectedly, the cells showed a large reduction of insulin gene expression, which was due to reduced insulin gene transcription. Electrophoretic mobility shift assays of PDX-1 binding to the insulin promoter A1 and E2/A3A4 elements showed additional bands indicating alterations of PDX-1 complex formation. Stable over expression of Ca(2+)/calmodulin-dependent protein kinase II delta(2), by contrast, was associated with elevated expression of insulin mRNA. Therefore, we conclude that Ca(2+)/calmodulin-dependent protein kinase II delta(2) links fuel-dependent increases in intracellular Ca(2+) concentrations to transcriptional regulation of genes related to the metabolic control of insulin secretion.

ATP-Binding Cassette Transporters↗
PubMed2002

[Disease prevention by vitamins and trace elements].

SUMMARY: Vitamins and trace elements are largely provided by a balanced nutrition. In industrialized countries, though, frequent deficiencies occur e.g. in folic acid and vitamin D as well as iodide, iron and calcium. A short review of recommended daily intake is presented.

Adolescent↗
PubMed2002

Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans.

The orexigenic and anabolic gastric hormone ghrelin is secreted in response to acute and chronic energy requirements. While pre-prandial increases and post-prandial decreases of plasma ghrelin levels in rodents and humans seem to indicate a role for the novel peptide hormone as an afferent meal initiator or "hunger hormone", the precise mechanisms which are suppressing ghrelin secretion in response to caloric intake remain largely unknown. We show here that human ghrelin levels decrease by almost 50% under hyperinsulinemic euglycemic clamp conditions (no.=4, p=0.001), revealing physiologically relevant increases of insulin levels as an independent determinant of circulating ghrelin levels. In a second study, 3-4-fold increased plasma free fatty acid levels, as another metabolic candidate for the modulation of circulating ghrelin concentrations, were generated by constant lipid infusion, but failed to change plasma ghrelin. Simultaneous elevation of free fatty acids and insulin again markedly decreased ghrelin concentration (no.=4, p=0.01). Insulin induced suppression of circulating ghrelin levels (or the lack thereof) could be a mechanism with relevance for the understanding of the (patho-) physiology of meal initiation and termination, the pathogenesis of the metabolic syndrome and for the development of respective therapeutic perspectives.

Adult↗
PubMed2002

Effects of the putatively oncogenic protein kinase Calpha D294G mutation on enzymatic activity and cell growth and its occurrence in human thyroid neoplasias.

A point mutation of protein kinase Calpha (PKCalpha) has been described in pituitary adenomas and in follicular adenomas and thyroid carcinomas. The mutation results in an exchange of aspartic acid into a glycine of the amino acid 294 of PKCalpha, which is located adjacent to the Ca (2+)-binding hinge region and has been proposed as an activation inhibitor. To investigate its biochemical sequelae, we constructed the mutated enzyme and expressed it in human embryonic kidney cells (HEK). The K M of the purified enzyme for Ca (2+) and its K M for the substrate MBP 4 - 14 was not altered by the mutation. Translocation of PKCalpha to HEK cell membranes upon activation was not changed and the mutant potently inhibited cell proliferation upon 5-fold stable overexpression in HEK cells. Thus, loss of function in mutated PKCalpha was excluded. A screen for the mutation using a restriction assay with a sensitivity of at least 8 % for the mutated DNA did not show any mutation in 11 carcinoma and 13 adenomatous thyroid samples. We conclude that the A294G mutation of PKCalpha does not detectably affect its biochemical properties in vitro or in vivo, and is at least rare in thyroid neoplasias, in Germany.

Biological Transport↗
PubMedDate not supplied

Insulin decreases human adiponectin plasma levels.

Insulin resistance and hyperinsulinemia are known atherosclerosis risk factors. The association between adiponectin plasma levels and obesity, insulinemia, and atherosclerosis has been shown. Thus, adiponectin may be a link between hyperinsulinemia and vascular disease. In vitro data demonstrated a reduction of adiponectin expression by insulin. However, it is still unclear whether insulin regulates adiponectinemia in vivo in humans. Five healthy male volunteers were studied. Circulating adiponectin levels were determined before and during hyperinsulinemic euglycemic clamp. Adiponectin was measured by radioimmunoassay. Hyperinsulinemia (85.0 +/- 33.2 at baseline vs. 482.8 +/- 64.4 pmol/l during steady state; p < 0.01) was achieved using a euglycemic hyperinsulinemic clamp, keeping blood glucose levels basically unchanged during the intervention (4.6 +/- 0.14 vs. 4.37 +/- 0.15 mmol/l, respectively; ns). We found a significant decrease of adiponectin plasma levels during the steady state of hyperinsulinemic euglycemic clamp (26.7 +/- 3.5 micro g/ml) compared to baseline levels (30.4 +/- 5 micro g/ml; p < 0.05). Hyperinsulinemia caused a significant decrease of adiponectin plasma levels under euglycemic conditions. Considering existing data about adiponectin dependent effects, hypoadiponectinemia might at least partly be a link between hyperinsulinemia and vascular disease in metabolic syndrome.

Adiponectin↗