Growth hormone receptor in VGLUT2 or Sim1 cells regulates glycemia and insulin sensitivity.

Growth hormone (GH) has several metabolic effects, including a profound impact on glucose homeostasis. For example, GH oversecretion induces insulin resistance and increases the risk of developing diabetes mellitus. Here, we show that GH receptor (GHR) ablation in vesicular glutamate transporter 2 (VGLUT2)-expressing cells, which comprise a subgroup of glutamatergic neurons, led to a slight decrease in lean body mass without inducing changes in body adiposity.

Effects of Branched-Chain Amino Acids on the Inflammatory Response Induced by LPS in Caco-2 Cells.

Branched-chain amino acids (BCAA) are essential for maintaining intestinal mucosal integrity. However, only a few studies have explored the role of BCAA in the modulation of intestinal inflammation. In this study, we investigated in vitro effects of BCAA on the inflammatory response induced by lipopolysaccharide (LPS) (1 µg/mL) in Caco-2 cells.

Estradiol Protects Female ApoE KO Mice against Western-Diet-Induced Non-Alcoholic Steatohepatitis.

Unlabelled: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its severe form, non-alcoholic steatohepatitis (NASH), is higher in men than in women of reproductive age, and postmenopausal women are especially susceptible to developing the disease.

Aim: we evaluated if female apolipoprotein E (ApoE) KO mice were protected against Western-diet (WD)-induced NASH.

Methods: Female ovariectomized (OVX) ApoE KO mice or sham-operated (SHAM) mice were fed either a WD or a regular chow (RC) for 7 weeks.

Low Birth Weight Intensifies Changes in Markers of Hepatocarcinogenesis Induced by Fructose Consumption in Rats.

Intrauterine growth restriction (IUGR) due to fetal exposure to glucocorticoid excess results in metabolic inflexibility and hepatic steatosis upon nutritional stress during adulthood. We previously demonstrated that rats born to dexamethasone (DEX)-treated mothers developed hepatic steatosis when exposed to 10% fructose solution during adult life. Persistent triacylglyceride (TAG) accumulation in the liver, in turn, is a feature of non-alcoholic fatty liver disease (NAFLD), which serves as a risk factor for non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC).

Western Diet-Fed ApoE Knockout Male Mice as an Experimental Model of Non-Alcoholic Steatohepatitis.

One of the consequences of the Western lifestyle and high-fat diet is non-alcoholic fatty liver disease (NAFLD) and its aggressive form, non-alcoholic steatohepatitis (NASH), which can progress to cirrhosis and hepatocellular carcinoma (HCC) and is rapidly becoming the leading cause of end-stage liver disease or liver transplantation. Currently, rodent NASH models lack significant aspects of the full NASH spectrum, representing a major problem for NASH research. Therefore, this work aimed to characterize a fast rodent model with all characteristic features of NASH.

Regulation of kidney mitochondrial function by caloric restriction.

Caloric restriction (CR) prevents obesity and increases resilience against pathological stimuli in laboratory rodents. At the mitochondrial level, protection promoted by CR in the brain and liver is related to higher Ca uptake rates and capacities, avoiding Ca-induced mitochondrial permeability transition. Dietary restriction has also been shown to increase kidney resistance against damaging stimuli; if these effects are related to similar mitochondrial adaptations has not been uncovered.

Disruption of polycystin-1 cleavage leads to cardiac metabolic rewiring in mice.

Cardiovascular manifestations account for marked morbi-mortality in autosomal dominant polycystic kidney disease (ADPKD). Pkd1- and Pkd2-deficient mice develop cardiac dysfunction, however the underlying mechanisms remain largely unclear. It is unknown whether impairment of polycystin-1 cleavage at the G-protein-coupled receptor proteolysis site, a significant ADPKD mutational mechanism, is involved in this process.

Ppia is the most stable housekeeping gene for qRT-PCR normalization in kidneys of three Pkd1-deficient mouse models.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most common inherited renal disorder, characterized by renal cyst development leading to end-stage renal disease. Although the appropriate choice of suitable reference is critical for quantitative RNA analysis, no comparison of frequently used "housekeeping" genes is available. Here, we determined the validity of 7 candidate housekeeping genes (Actb, Actg1, B2m, Gapdh, Hprt, Pgam1 and Ppia) in kidney tissues from mouse models orthologous to ADPKD, including a cystic mice (CY) 10-12 weeks old (Pkd1:Nestin/Pkd1:Nestin, n = 10) and non-cystic (NC) controls (Pkd1//Pkd1/, n = 10), Pkd1-haploinsufficient (HT) mice (Pkd1, n = 6) and wild-type (WT) controls (Pkd1, n = 6) and a severely cystic (SC) mice 15 days old (Pkd1, n = 7) and their controls (CO, n = 5).

Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice.

Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13-18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals.

Fructose Consumption by Adult Rats Exposed to Dexamethasone In Utero Changes the Phenotype of Intestinal Epithelial Cells and Exacerbates Intestinal Gluconeogenesis.

Fructose consumption by rodents modulates both hepatic and intestinal lipid metabolism and gluconeogenesis. We have previously demonstrated that in utero exposure to dexamethasone (DEX) interacts with fructose consumption during adult life to exacerbate hepatic steatosis in rats. The aim of this study was to clarify if adult rats born to DEX-treated mothers would display differences in intestinal gluconeogenesis after excessive fructose intake.

Influence of androgenic blockade with flutamide on pain behaviour and expression of the genes that encode the NaV1.7 and NaV1.8 voltage-dependent sodium channels in a rat model of postoperative pain.

Background: Experimental studies suggest that testosterone reduces the nociceptive response after inflammatory and neuropathic stimuli, however the underlying mechanisms have not been fully elucidated. The aims of this study were to evaluate the effect of peripheral blockade of testosterone on pain behaviour and on expression levels of the genes that encode the NaV1.7 and NaV1.

Cardiac dysfunction in Pkd1-deficient mice with phenotype rescue by galectin-3 knockout.

Alterations in myocardial wall texture stand out among ADPKD cardiovascular manifestations in hypertensive and normotensive patients. To elucidate their pathogenesis, we analyzed the cardiac phenotype in Pkd1(cond/cond)Nestin(cre) (CYG+) cystic mice exposed to increased blood pressure, at 5 to 6 and 20 to 24 weeks of age, and Pkd1(+/-) (HTG+) noncystic mice at 5-6 and 10-13 weeks. Echocardiographic analyses revealed decreased myocardial deformation and systolic function in CYG+ and HTG+ mice, as well as diastolic dysfunction in older CYG+ mice, compared to their Pkd1(cond/cond) and Pkd1(+/+) controls.

Regulation of CFTR Expression and Arginine Vasopressin Activity Are Dependent on Polycystin-1 in Kidney-Derived Cells.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the development of multiple, progressive, fluid-filled renal cysts that distort the renal parenchyma, leading to end-stage renal failure, mainly after the fifth decade of life. ADPKD is caused by a mutation in the PKD1 or PKD2 genes that encode polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively. PC-1 is an important regulator of several signaling pathways and PC-2 is a nonselective calcium channel.

Renal cyst growth is the main determinant for hypertension and concentrating deficit in Pkd1-deficient mice.

We have bred a Pkd1 floxed allele with a nestin-Cre expressing line to generate cystic mice with preserved glomerular filtration rate to address the pathogenesis of complex autosomal dominant polycystic kidney disease (ADPKD) phenotypes. Hypertension affects about 60% of these patients before loss of renal function, leading to significant morbimortality. Cystic mice were hypertensive at 5 and 13 weeks of age, a phenotype not seen in noncystic controls and Pkd1-haploinsufficient animals that do not develop renal cysts.

Taurine supplementation restores insulin secretion and reduces ER stress markers in protein-malnourished mice.

Endoplasmic reticulum (ER) stress is a cellular response to increased intra-reticular protein accumulation or poor ER function. Chronic activation of this pathway may lead to beta cell death and metabolic syndrome (MS). Poor nutrition during perinatal period, especially protein malnutrition, is associated with increased risk for MS in later life.

Taurine supplementation restores glucose and carbachol-induced insulin secretion in islets from low-protein diet rats: involvement of Ach-M3R, Synt 1 and SNAP-25 proteins.

Isolated islets from low-protein (LP) diet rats showed decreased insulin secretion in response to glucose and carbachol (Cch). Taurine (TAU) increases insulin secretion in rodent islets with a positive effect upon the cholinergic pathway. Here, we investigated the effect of TAU administration upon glucose tolerance and insulin release in rats fed on a normal protein diet (17%) without (NP) or with 2.

Leucine supplementation augments insulin secretion in pancreatic islets of malnourished mice.

Objectives: We investigated the influence of leucine supplementation on insulin secretion and on some proteins related to insulin secretion in malnourished mice.

Methods: Swiss mice (aged 21 days) received isocaloric normo-17% (NP) or 6% low-protein (LP) diet for 120 days. Half of the NP and LP mice received 1.

Reduced insulin secretion in protein malnourished mice is associated with multiple changes in the beta-cell stimulus-secretion coupling.

The mechanism by which protein malnutrition impairs glucose-stimulated insulin secretion in the pancreatic beta-cell is not completely known but may be related to alterations in the signaling events involved in insulin release. Here, we aimed to study the stimulus-secretion coupling of beta-cells from mice fed with low-protein (LP) diet or normal-protein (NP) diet for 8 wk after weaning. Patch-clamp measurements in isolated cells showed that beta-cells from LP mice had a resting membrane potential that was more hyperpolarized than controls.

Taurine supplementation enhances nutrient-induced insulin secretion in pancreatic mice islets.

Background: Taurine (TAU), a naturally occurring sulfur-containing amino acid, is found at high concentrations in plasma and mammalian tissues and regulates osmolarity, ion channel activity, and glucose homeostasis. Several reports have shown that physiological plasma TAU levels seem to be important for adequate beta (beta)-cell function and insulin action, since low concentrations of TAU in the plasma have been reported in the pre-diabetic and diabetic states.

Methods: Glucose tolerance and insulin sensitivity were investigated in mice supplemented with 2% (w/v) TAU in their drinking water for 30 days, as well as the insulin secretion from isolated islets stimulated by glucose or L-leucine.