Liminal gastrin does not activate rat stomach histidine decarboxylase

Summary Fasted rats have a low gastric histidine decarboxylase activity. I.v. infusion of heptadecapeptide gastrin for 2 h raised the enzyme activity. Intragastric perfusion with the same dose of gastrin and for the same period of time did not reproduce the effect of circulating gastrin. It is concluded that luminal gastrin, in contrast to circulating gastrin, does not activate rat stomach histidine decarboxylase.This study was supported by the Swedish Medical Research Council (04X-1007, 14X-4144) and by the Albert Påhlsson Foundation.     

Histidine decarboxylase and DOPA decarboxylase in the stomach of the developing rat

Zusammenfassung Im Magen der fötalen Ratte erreicht die Dopadecarboxylase-Aktivität 19 Tage nach der Paarung Werte, die den Aktivitätswerten des erwachsenen Tieres entsprechen. Die Aktivität bleibt auch während der weiteren Entwicklung hoch. Die Histidindecarboxylase des fötalen Rattenmagens ist während der embryonalen Entwicklung hoch, aber die Aktivitätswerte fallen bei der Geburt zu nicht messbaren Werten ab. Ungefähr 8 Tage post partum steigt die Histidindecarboxylase des Magens wieder an und erreicht einen Monat nach der Geburt Werte, die den Aktivitätswerten des erwachsenen Tieres entsprechen. In der jungen Ratte wird die Magenhistidindecarboxylase weder durch Gastrininjektion noch durch Hungern beeinträchtigt. Vom 18. Tag nach der Geburt an kann die Enzymaktivität durch Hungern verringert und durch Gastrin wieder erhöht werden.     

Occurrence of insulin in rat duodenum and its depletion with alloxan

Resumé Un taux faible d'insuline immunoréactive (IRI) et d'activité semblable à l'insuline (ILA) a été décelé dans la muqueuse duodénale du rat, mais non pas dans celles du lapin, du chat et du chien. Les autres régions du tractus digestif de toutes ces expèces présentaient un taux extrèmement bas d'insuline. Le traitement par l'alloxane entraîne le vidage de l'IRI et l'ILA duodénales.     

Pricing of basket options using univariate normal inverse Gaussian approximations

In this paper we study the approximation of a sum of assets having marginal log‐returns being multivariate normal inverse Gaussian distributed. We analyse the choice of a univariate exponential NIG distribution, where the approximation is based on matching of moments. Probability densities and European basket call option prices of the two‐asset and univariate approximations are studied and analysed in two cases, each case consisting of nine scenarios of different volatilities and correlations, to assess the accuracy of the approximation. We find that the sum can be well approximated, failing, however, to match the tails for some extreme parameter choices. The approximated option prices are close to the true ones, although becoming significantly underestimated for far out‐of‐the‐money call options. Copyright © 2010 John Wiley & Sons, Ltd.     

New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis

Leber congenital amaurosis (LCA) is the most serious form of the autosomal recessive childhood-onset retinal dystrophies. Mutations in the gene encoding RPE65, a protein vital for regeneration of the visual pigment rhodopsin in the retinal pigment epithelium, account for 10-15% of LCA cases. Whereas previous studies of RPE65 deficiency in both animal models and patients attributed remaining visual function to cones, we show here that light-evoked retinal responses in fact originate from rods. For this purpose, we selectively impaired either rod or cone function in Rpe65-/- mice by generating double- mutant mice with models of pure cone function (rhodopsin-deficient mice; Rho-/-) and pure rod function (cyclic nucleotide-gated channel alpha3-deficient mice; Cnga3-/-). The electroretinograms (ERGs) of Rpe65-/- and Rpe65-/-Cnga3-/- mice were almost identical, whereas there was no assessable response in Rpe65-/-Rho-/- mice. Thus, we conclude that the rod system is the source of vision in RPE65 deficiency. Furthermore, we found that lack of RPE65 enables rods to mimic cone function by responding under normally cone-isolating lighting conditions. We propose as a mechanism decreased rod sensitivity due to a reduction in rhodopsin content to less than 1%. In general, the dissection of pathophysiological processes in animal models through the introduction of additional, selective mutations is a promising concept in functional genetics.     

Activation of rat stomach histidine decarboxylase after inhibition of acid secretion with 2-Phenyl-2-(2-Pyridyl)-Thioacetamide (SC-15396)

Zusammenfassung 2-Phenyl-2(2-Pyridyl)-Thioacetamide (SC-15396) ist ein kräftiger Inhibitor von sowohl basaler als auch stimulierter gastrischer Säuresekretion und aktiviert die Histidindecarboxylase in der Magenschleimhaut. Die enzymaktivierende Wirkung von SC-15396 wird durch Resektion des Antrums verhindert. Daraus kann geschlossen werden, dass die durch SC-15396 hervorgerufene Enzymaktivierung eine Folge von erhöhter Freisetzung von antralem Gastrin ist.     

Spontaneous muscle twitches during sleep guide spinal self-organization

During development, information about the three-dimensional shape and mechanical properties of the body is laid down in the synaptic connectivity of sensorimotor systems through unknown adaptive mechanisms. In spinal reflex systems, this enables the fast transformation of complex sensory information into adequate correction of movements. Here we use a computer simulation to show that an unsupervised correlation-based learning mechanism, using spontaneous muscle twitches, can account for the functional adaptation of the withdrawal reflex system. We also show that tactile feedback resulting from spontaneous muscle twitches during sleep does indeed modify sensorimotor transformation in young rats in a predictable manner. The results indicate that these twitches, corresponding to human fetal movements, are important in spinal self-organization.     

Dynamics of fat cell turnover in humans

Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells (adipocytes) is thought to be most important. Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of 14C derived from nuclear bomb tests in genomic DNA. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.     

Specific cleavage of insulin-like growth factor-binding protein-1 by a novel protease activity

Insulin-like growth factor-binding protein-1 (IGFBP-1) is secreted in a highly phosphorylated form that binds IGF-I with high affinity and is resistant to proteolysis. We have purified IGFBP-1-specific protease activity from the urine of an individual with multiple myeloma. This protease efficiently cleaves both phosphorylated and non-phosphorylated IGFBP-1 at Ile130-Ser131, generating fragments that together have higher association and dissociation rates for IGFs compared with intact IGFBP-1. The proteolytic fraction contained azurocidin, a protease homologue hitherto considered inactive. After cleavage of IGFBP-1, there was a lower affinity, but higher capacity for IGF-I binding, suggesting both N- and C-terminal fragments may interact with ligand independently. There was decreased inhibition of IGF-II-stimulated cell growth and glucose uptake. Alone, proteolysed IGFBP-1 stimulated glucose uptake in muscle. We conclude that specific cleavage of IGFBP-1 at target tissues is important in cellular growth and metabolism and opens novel strategies for targeting IGFBP-1 in treatment of disease.