Clenbuterol exerts antidiabetic activity through metabolic reprogramming of skeletal muscle cells.

Activation of the sympathetic nervous system causes pronounced metabolic changes that are mediated by multiple adrenergic receptor subtypes. Systemic treatment with βadrenergic receptor agonists results in multiple beneficial metabolic effects, including improved glucose homeostasis. To elucidate the underlying cellular and molecular mechanisms, we chronically treated wild-type mice and several newly developed mutant mouse strains with clenbuterol, a selective β-adrenergic receptor agonist.

[Diagnosis and surgical treatment of acute destructive calculous cholecystitis in advanced age patients].

Objective: To develop an algorithm for surgical treatment of acute destructive cholecystitis in elderly and senile patients and to improve postoperative outcomes in this cohort of patients.

Material And Methods: A prospective analysis included 50 patients with acute destructive cholecystitis aged 60-90 years, who admitted to the Topchubashov Research Surgical Center for the period from 2015 to 2019. All patients had diabetes mellitus, obesity or cardiovascular diseases.

Imaging of Tissue-Specific and Temporal Activation of GPCR Signaling Using DREADD Knock-In Mice.

Engineered G protein-coupled receptors (DREADDs, designer receptors exclusively activated by designer drugs) are convenient tools for specific activation of GPCR signaling in many cell types. DREADDs have been utilized as research tools to study numerous cellular and physiologic processes, including regulation of neuronal activity, behavior, and metabolism. Mice with random insertion transgenes and adeno-associated viruses have been widely used to express DREADDs in individual cell types.

Prevalence of spinocerebellar ataxia 36 in a US population.

Objective: To assess the prevalence and clinical features of individuals affected by spinocerebellar ataxia 36 (SCA36) at a large tertiary referral center in the United States.

Methods: A total of 577 patients with undiagnosed sporadic or familial cerebellar ataxia comprehensively evaluated at a tertiary referral ataxia center were molecularly evaluated for SCA36. Repeat primed PCR and fragment analysis were used to screen for the presence of a repeat expansion in the gene.

Red blood cell β-adrenergic receptors contribute to diet-induced energy expenditure by increasing O2 supply.

Diet-induced obesity (DIO) represents the major cause for the current obesity epidemic, but the mechanism underlying DIO is unclear. β-Adrenergic receptors (β-ARs) play a major role in sympathetic nervous system-mediated (SNS-mediated) diet-induced energy expenditure (EE). Rbc express abundant β-ARs; however, a potential role for rbc in DIO remains untested.

Gs-DREADD Knock-In Mice for Tissue-Specific, Temporal Stimulation of Cyclic AMP Signaling.

Hundreds of hormones and ligands stimulate cyclic AMP (cAMP) signaling in different tissues through the activation of G-protein-coupled receptors (GPCRs). Although the functions and individual effectors of cAMP signaling are well characterized in many tissues, pleiotropic effects of GPCR agonists limit investigations of physiological functions of cAMP signaling in individual cell types at different developmental stages To facilitate studies of cAMP signaling in specific cell populations , we harnessed the power of DREADD (designer receptors exclusively activated by designer drugs) technology by creating -based knock-in mice for the conditional expression of a Gs-coupled DREADD (rM3Ds-green fluorescent protein [GFP], or "GsD"). After Cre recombinase expression, GsD is activated temporally by the administration of the ligand clozapine -oxide (CNO).

Correction: Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity.

[This corrects the article DOI: 10.1371/journal.pone.

Knock-in Luciferase Reporter Mice for In Vivo Monitoring of CREB Activity.

The cAMP response element binding protein (CREB) is induced during fasting in the liver, where it stimulates transcription of rate-limiting gluconeogenic genes to maintain metabolic homeostasis. Adenoviral and transgenic CREB reporters have been used to monitor hepatic CREB activity non-invasively using bioluminescence reporter imaging. However, adenoviral vectors and randomly inserted transgenes have several limitations.

Skeletal muscle salt inducible kinase 1 promotes insulin resistance in obesity.

Objective: Insulin resistance causes type 2 diabetes mellitus and hyperglycemia due to excessive hepatic glucose production and inadequate peripheral glucose uptake. Our objectives were to test the hypothesis that the proposed CREB/CRTC2 inhibitor salt inducible kinase 1 (SIK1) contributes to whole body glucose homeostasis in vivo by regulating hepatic transcription of gluconeogenic genes and also to identify novel SIK1 actions on glucose metabolism.

Methods: We created conditional (floxed) SIK1-knockout mice and studied glucose metabolism in animals with global, liver, adipose or skeletal muscle Sik1 deletion.

Diminished MTORC1-Dependent JNK Activation Underlies the Neurodevelopmental Defects Associated with Lysosomal Dysfunction.

Here, we evaluate the mechanisms underlying the neurodevelopmental deficits in Drosophila and mouse models of lysosomal storage diseases (LSDs). We find that lysosomes promote the growth of neuromuscular junctions (NMJs) via Rag GTPases and mechanistic target of rapamycin complex 1 (MTORC1). However, rather than employing S6K/4E-BP1, MTORC1 stimulates NMJ growth via JNK, a determinant of axonal growth in Drosophila and mammals.

The effects of obesity on skeletal muscle regeneration.

Obesity and metabolic disorders such as type 2 diabetes mellitus are accompanied by increased lipid deposition in adipose and non-adipose tissues including liver, pancreas, heart and skeletal muscle. Recent publications report impaired regenerative capacity of skeletal muscle following injury in obese mice. Although muscle regeneration has not been thoroughly studied in obese and type 2 diabetic humans and mechanisms leading to decreased muscle regeneration in obesity remain elusive, the initial findings point to the possibility that muscle satellite cell function is compromised under conditions of lipid overload.

The short isoform of the ubiquitin ligase NEDD4L is a CREB target gene in hepatocytes.

During cycles of fasting and feeding, liver function is regulated by both transcriptional and post-translational events. Regulated protein degradation has recently emerged as a key mechanism to control abundance of specific hepatic proteins under different nutritional conditions. As glucagon signaling through cAMP and PKA is central to glucose output during fasting, we hypothesized that this signaling pathway may also regulate ubiquitin ligases in the fasted state.

[The allergy diagnostic of brucellosis].

The infectious allergy plays an important role in the pathogenesis of brucellosis. In the allergy diagnostic of toxoplasmosis the cell reactions in vivo are equally applied with the Burnet intradermal allergic test. In the present study the reaction of leukolysis was applied to detect the sensibilization of leucocytes in blood and saliva under brucellosis.

Regulation of SIK1 abundance and stability is critical for myogenesis.

cAMP signaling can both promote and inhibit myogenic differentiation, but little is known about the mechanisms mediating promyogenic effects of cAMP. We previously demonstrated that the cAMP response element-binding protein (CREB) transcriptional target salt-inducible kinase 1 (SIK1) promotes MEF2 activity in myocytes via phosphorylation of class II histone deacetylase proteins (HDACs). However, it was unknown whether SIK1 couples cAMP signaling to the HDAC-MEF2 pathway during myogenesis and how this response could specifically occur in differentiating muscle cells.

Pyruvate dehydrogenase E1α phosphorylation is induced by glucose but does not control metabolism-secretion coupling in INS-1E clonal β-cells.

Glucose-induced insulin secretion from pancreatic β-cells depends on mitochondrial activation. In the organelle, glucose-derived pyruvate is metabolised along the oxidative and anaplerotic pathway to generate downstream signals leading to insulin granule exocytosis. Entry into the oxidative pathway is catalysed by pyruvate dehydrogenase (PDH) and controlled in part by phosphorylation of the PDH E1α subunit blocking enzyme activity.

Hepatic nuclear factor 1alpha (HNF1alpha) dysfunction down-regulates X-box-binding protein 1 (XBP1) and sensitizes beta-cells to endoplasmic reticulum stress.

Correct endoplasmic reticulum (ER) function is critical for the health of secretory cells, such as the pancreatic β-cell, and ER stress is often a contributory factor to β-cell death in type 2 diabetes. We have used an insulin-secreting cell line with inducible expression of dominant negative (DN) HNF1α, a transcription factor vital for correct β-cell development and function, to show that HNF1α is required for Xbp1 transcription and maintenance of the normal ER stress response. DN HNF1α expression sensitizes the β-cell to ER stress by directly down-regulating Xbp1 transcription, whereas Atf6 is unaffected.

Mitochondrial matrix calcium is an activating signal for hormone secretion.

Mitochondrial Ca(2+) signals have been proposed to accelerate oxidative metabolism and ATP production to match Ca(2+)-activated energy-consuming processes. Efforts to understand the signaling role of mitochondrial Ca(2+) have been hampered by the inability to manipulate matrix Ca(2+) without directly altering cytosolic Ca(2+). We were able to selectively buffer mitochondrial Ca(2+) rises by targeting the Ca(2+)-binding protein S100G to the matrix.

Mitochondrial matrix pH controls oxidative phosphorylation and metabolism-secretion coupling in INS-1E clonal beta cells.

Glucose-evoked mitochondrial signals augment ATP synthesis in the pancreatic β cell. This activation of energy metabolism increases the cytosolic ATP/ADP ratio, which stimulates plasma membrane electrical activity and insulin granule exocytosis. We have recently demonstrated that matrix pH increases during nutrient stimulation of the pancreatic β cell.

[Comparative information value of humoral immunity characteristics in some bacterial and viral infections].

Serological examination of 144 patients with different bacterial and viral infections was carried out. Antibodies to Brucella were detected in blood serum in 42 patients (85.7%) with the average titer of 1:996 and in saliva in 41 patients (83.

[Functional and metabolic activity of leukocytes in patients with chronic brucellosis].

Aim: Investigation of functional-metabolic activity of leukocytes by assessment of basic components of the microbicidal system in the course of chronic brucellosis with reference to the stage, severity, complications and concomitant diseases.

Material And Methods: Time course of changes in myeloperoxidase, acid and alkaline phosphatase activity, levels of cation protein, glycogen and lipids in leukocytes were studied in seventy-one 16-70-year-old patients with exacerbation of chronic brucellosis. The diagnosis of primary-chronic, secondary-chronic brucellosis, subcompensation was made in 13, 58 and 69 patients, respectively.

[The immune status of patients with typhoid fever].

The immune status in 48 typhoid fever (TF) patients has been studied. As revealed in this study, during the fever period of the disease pronounced disturbances in immune homeostasis are observed, which are manifested by T lymphopenia, the prevalence of suppressor subpopulations of T lymphocytes with the prevalence of T helpers, a considerable rise in the level of circulating immune complexes (CIC), mainly highly pathogenic medium- and low-molecular complexes. At the early period of convalescence the preservation of all these signs is indicative of fact that the treat of TF relapse is present.

[The status of the blood antioxidant system in a chronic typhoid bacterial carrier state].

The problems dealt with in this work, the study of the pathogenesis of chronic Salmonella typhi carriership and the development of preparations for its sanation, are highly topical. The data on the evaluation of the state of antioxidative system in 33 chronic S. typhi carriers are presented.

[A device for de-epithelization of the skin for skin scarification tests].

The characteristic feature of the suggested device is the presence of a safety lock limiting a forward motion of the de-epithelializer into the depth of the epidermis; this rules out injuries of small vessels and provides the necessary depth of the epithelium removal. The device is recommended for skin allergic scarification tests and for Rebuck's skin fenestra test.