The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD). In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP(swe)/PS1(dE9) transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma Aβ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF Aβ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma Aβ, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on Aβ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate Aβ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma Aβ in young and old mice, independent of neuronal insulin signaling. SIGNIFICANCE STATEMENT The transportation of insulin from blood to brain is a saturable process relevant to understanding the link between hyperinsulinemia and AD. In vitro experiments have found direct connections between high insulin and extracellular Aβ, but these mechanisms presume that peripheral high insulin elevates brain insulin significantly. We found that physiological hyperinsulinemia in awake, behaving mice does not increase CNS insulin to an appreciable level yet modestly increases extracellular Aβ. We also found that the brain of aged APP/PS1 mice was not insulin resistant, contrary to the current state of the literature. These results further elucidate the relationship between insulin, the brain, and AD and its conflicting roles as both a risk factor and potential treatment

Cloning crops in a CELSS via tissue culture: Prospects and problems

Micropropagation is currently used to clone fruits, nuts, and vegetables and involves controlling the outgrowth in vitro of basal, axillary, or adventitious buds. Following clonal multiplication, shoots are divided and rooted. This process has greatly reduced space and energy requirements in greenhouses and field nurseries and has increased multiplication rates by greater than 20 fold for some vegetatively propagated crops and breeding lines. Cereal and legume crops can also be cloned by tissue culture through somatic embryogenesis. Somatic embryos can be used to produce 'synthetic seed', which can tolerate desiccation and germinate upon rehydration. Synthetic seed of hybrid wheat, rice, soybean and other crops could be produced in a controlled ecological life support system. Thus, yield advantages of hybreds over inbreds (10 to 20 percent) could be exploited without having to provide additional facilities and energy for parental-line and hybrid seed nurseries

Influence of arbuscular mycorrhizal fungi genera Glomus on growth and development of rootstoch MrS 2/5 (Prunus cerasifera L.)

U ovom istraživanju proučavan je utjecaj četiriju izolata arbuskularno-mikoriznih gljiva Glomus mossae, G. intraradices, G.coronatum i G. viscosum na rast i razvoj podloge MrS 2/5 (Prunus cerasifera L.). Na osnovi dobivenih rezultata istraživanja možemo ustvrditi kako su svi inokulirani tretmani postigli veće vrijednosti mjerenih parametara u odnosu na kontrolne neinokulirane. To se posebno odnosi na postotak preživljavanja transplantacijskog stresa koji se kod kontrolnih biljaka kretao oko 60 %, dok je kod inokuliranih biljaka bio između 80 i 90 %. G.mossae pokazao se kao najuspješnija kombinacija s odabranom podlogom, no odmah iza njega je bio G.coronatum, tako da u nekim mjerenim parametrima među njima nije bilo statistički opravdane razlike. Najslabije rezultate unutar inokuliranih podloga imale su one tretirane s G. viscosum.This research studied influence of four arbuscular mycorrhizal fungi isolates of Glomus mossae, G. intraradices, G.coronatum and G. viscosum on growth and development of rootstock MrS 2/5 (Prunus cerasifera L.). Inoculated treatments showed improved plant growth and development in comparison with those uninoculated. This can especially be seen in the survival percentage of transplantation stress, which was 60 % for the control and between 80-90 % for inoculated plants. The most effective symbiotic combination was host rootstock with G.mossae, however G.coronatum was also a succefulss combination and in some investigated parameters there was no significant difference between them. Among inoculated rootstocks those treated with G. viscosum were the least effective

Leptin-dependent Phosphorylation of PTEN Mediates Actin Restructuring and Activation of ATP-sensitive K+ Channels

Leptin activates multiple signaling pathways in cells, including the phosphatidylinositol 3-kinase pathway, indicating a degree of cross-talk with insulin signaling. The exact mechanisms by which leptin alters this signaling pathway and how it relates to functional outputs are unclear at present. A previous study has established that leptin inhibits the activity of the phosphatase PTEN (phosphatase and tensin homolog deleted on chromosome 10), an important tumor suppressor and modifier of phosphoinositide signaling. In this study we demonstrate that leptin phosphorylates multiple sites on the C-terminal tail of PTEN in hypothalamic and pancreatic β-cells, an action not replicated by insulin. Inhibitors of the protein kinases CK2 and glycogen synthase kinase 3 (GSK3) block leptin-mediated PTEN phosphorylation. PTEN phosphorylation mutants reveal the critical role these sites play in transmission of the leptin signal to F-actin depolymerization. CK2 and GSK3 inhibitors also prevent leptin-mediated F-actin depolymerization and consequent ATP-sensitive K+ channel opening. GSK3 kinase activity is inhibited by insulin but not leptin in hypothalamic cells. Both hormones increase N-terminal GSK3 serine phosphorylation, but in hypothalamic cells this action of leptin is transient. Leptin, not insulin, increases GSK3 tyrosine phosphorylation in both cell types. These results demonstrate a significant role for PTEN in leptin signal transmission and identify GSK3 as a potential important signaling node contributing to divergent outputs for these hormones

Rhodora

v.52 (1950

GENETIC AND CHEMICAL APPROACHES TO MANAGE RYE LEAF RUST (PUCCINIA RECONDITA F.SP. SECALIS) IN NATURAL CONDITIONS FROM MARGINAL AREAS

Pathogens and pests are predicted to spread to areas where they were previously irrelevant due to climate change and human-induced changes, posing new management issues for crops, especially in cropping systems based on minimal cereal crop diversification. In temperate areas of Central and Eastern Europe, rye (Secale cereale) is a minor cereal that contributes to crops diversification particularly in marginal situations where soil and climate are unfavorable for wheat production. During 2021-2022 growing season, a plant–pest-pathogen interaction profile was observed on four rye genotypes (Binnto, Inspector, Serafino, Suceveana) and also was observed the effect of different chemical and biological pesticide formulations on rye leaf rust in a randomized complete block design with three replications in dry area from Research and Development Station for Plant Culture on Sands Dăbuleni in South of Romania. Among all evaluated rye genotypes the greatest resistance was noticed in Serafino that recorded the lowest AUDPC value (51,76), while the most susceptible was Suceveana genotype with AUDPC = 279,55.  The best protection against leaf rust was provided by Poliversum (the 1st assessment – attack degree = 3,23%; the 2nd assessment – attack degree = 7,56%). Negative and significant correlation of leaf rust attack degrees with grain yield (r =-0,9393***) were found during 2021-2022 cropping season

Novel roles for JNK1 in metabolism

Activation of stress-kinase signaling has recently been recognized as an important pathophysiological mechanism in the development of diet-induced obesity, type 2 diabetes mellitus and other aging-related pathologies. Here, c-Jun N-terminal Kinase (JNK) 1 knockout mice have been shown to exhibit protection from diet-induced obesity, glucose intolerance, and insulin resistance. Nonetheless, the tissue-specific role of JNK1-activation in the development of the metabolic syndrome has been poorly defined so far. Recently, it was demonstrated that JNK1 signaling plays a crucial role in the central nervous system (CNS) and in the pituitary to control systemic glucose and lipid metabolism partially through regulation of hormones involved in growth and energy expenditure

Investigations into the absorption of insulin and insulin derivatives from the small intestine of the anaesthetised rat

Experiments have been undertaken to determine the extent to which cholic acid conjugates of insulin were absorbed from the small intestine of anaesthetised rats by means of the bile salt transporters of the ileum. The measure used to assess the absorption of the cholyl-insulins was the amount of hypoglycaemia following infusion into the small intestine. Control experiments involving infusion of natural insulin into the ileum showed either nil absorption or absorption of a small amount of insulin as indicated by transient dip in the blood glucose concentration. However, when insulin was co-infused with the bile salt taurocholate, this was followed by a marked hypoglycaemic response which was specific to the ileum and did not occur on infusion into the jejunum. When the two cholyl conjugates of insulin were tested viz. B 29-Lys-cholyl-insulin and B 1-Phe-cholyl-insulin, both were biologically active as indicated by hypoglycaemic responses on systemic injection, though their potency was about 40% of that of natural insulin. While there was no evidence for the absorption of B 29-Lys-cholyl-insulin when infused into the ileum, B 1-Phe-cholyl-insulin did cause a long lasting hypoglycaemic response, indicating that absorption had occurred. Since the hypoglycaemic response was blocked on co-infusion with taurocholate and was absent for infusion of the conjugate into the jejunum, these results were taken as evidence that B 1-Phe-cholyl-insulin had been taken up by the ileal bile salt transporters. This would indicate that B 1-Phe-cholyl-insulin is worthy of further investigation for use in an oral insulin formulation