scholarly journals The Candidate Schizophrenia Risk Gene Tmem108 Regulates Glucose Metabolism Homeostasis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jianbo Yu ◽  
Xufeng Liao ◽  
Yanzi Zhong ◽  
Yongqiang Wu ◽  
Xinsheng Lai ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Transmembrane Protein ◽  
Sensorimotor Gating ◽  
Pathological Process ◽  
Mutant Mice ◽  
Psychiatric Disease ◽  
Glucose Levels ◽  
Risk Gene ◽  
Urine Production ◽  
Susceptible Gene

BackgroundSchizophrenia (SCZ) is a severe psychiatric disease affected by genetic factors and environmental contributors, and premorbid abnormality of glucose metabolism is one of the SCZ characteristics supposed to contribute to the disease’s pathological process. Transmembrane protein 108 (Tmem108) is a susceptible gene associated with multiple psychiatric diseases, including SCZ. Moreover, Tmem108 mutant mice exhibit SCZ-like behaviors in the measurement of sensorimotor gating. However, it is unknown whether Tmem108 regulates glucose metabolism homeostasis while it involves SCZ pathophysiological process.ResultsIn this research, we found that Tmem108 mutant mice exhibited glucose intolerance, insulin resistance, and disturbed metabolic homeostasis. Food and oxygen consumption decreased, and urine production increased, accompanied by weak fatigue resistance in the mutant mice. Simultaneously, the glucose metabolic pathway was enhanced, and lipid metabolism decreased in the mutant mice, consistent with the elevated respiratory exchange ratio (RER). Furthermore, metformin attenuated plasma glucose levels and improved sensorimotor gating in Tmem108 mutant mice.ConclusionsHyperglycemia occurs more often in SCZ patients than in control, implying that these two diseases share common biological mechanisms, here we demonstrate that the Tmem108 mutant may represent such a comorbid mechanism.

scholarly journals Examination of Potential Mechanisms in the Enhancement of Cerebral Blood Flow by Hypoglycemia and Pharmacological Doses of Deoxyglucose

1997 ◽  
Vol 17 (1) ◽  
pp. 54-63 ◽  
Author(s):  
Naoaki Horinaka ◽  
Nicole Artz ◽  
Jane Jehle ◽  
Shinichi Takahashi ◽  
Charles Kennedy ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Glucose Metabolism ◽  
Plasma Glucose ◽  
Plasma Lactate ◽  
Insulin Hypoglycemia ◽  
Glucose Levels ◽  
Arterial Blood ◽  
Arterial Plasma

Cerebral blood flow (CBF) rises when the glucose supply to the brain is limited by hypoglycemia or glucose metabolism is inhibited by pharmacological doses of 2-deoxyglucose (DG). The present studies in unanesthetized rats with insulin-induced hypoglycemia show that the increases in CBF, measured with the [14C]iodoantipyrine method, are relatively small until arterial plasma glucose levels fall to 2.5 to 3.0 m M, at which point CBF rises sharply. A direct effect of insulin on CBF was excluded; insulin administered under euglycemic conditions maintained by glucose injections had no effects on CBF. Insulin administration raised plasma lactate levels and decreased plasma K+ and HCO3– concentrations and arterial pH. These could not, however, be related to the increased CBF because insulin under euglycemic conditions had similar effects without affecting CBF; furthermore, the inhibition of brain glucose metabolism with pharmacological doses (200 mg/kg intravenously) of DG increased CBF, just like insulin hypoglycemia, without altering plasma lactate and K+ levels and arterial blood gas tensions and pH. Nitric oxide also does not appear to mediate the increases in CBF. Chronic blockade of nitric oxide synthase activity by twice daily i.p. injections of NG-nitro-L-arginine methyl ester for 4 days or acutely by a single i.v. injection raised arterial blood pressure and lowered CBF in normoglycemic, hypoglycemic, and DG-treated rats but did not significantly reduce the increases in CBF due to insulin-induced hypoglycemia (arterial plasma glucose levels, 2.5-3 m M) or pharmacological doses of deoxyglucose.

Effects of MDMA on blood glucose levels and brain glucose metabolism

2007 ◽  
Vol 34 (6) ◽  
pp. 916-925 ◽  
Author(s):  
M. L. Soto-Montenegro ◽  
J. J. Vaquero ◽  
C. Arango ◽  
G. Ricaurte ◽  
P. García-Barreno ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glucose Metabolism ◽  
Brain Glucose ◽  
Brain Glucose Metabolism ◽  
Glucose Levels ◽  
Blood Glucose Levels

Antibiotic-induced microbiome depletion alters renal glucose metabolism and exacerbates renal injury after ischemia-reperfusion injury in mice

2021 ◽  
Author(s):  
Yuika Osada ◽  
Shunsaku Nakagawa ◽  
Kanako Ishibe ◽  
Shota Takao ◽  
Aimi Shimazaki ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Kidney Injury ◽  
Short Chain Fatty Acids ◽  
Glucose Levels ◽  
The Impact

Recent studies have revealed the impact of antibiotic-induced microbiome depletion (AIMD) on host glucose homeostasis. The kidney has a critical role in systemic glucose homeostasis; however, information regarding the association between AIMD and renal glucose metabolism remains limited. Hence, we aimed to determine the effects of AIMD on renal glucose metabolism by inducing gut microbiome depletion using an antibiotic cocktail (ABX) composed of ampicillin, vancomycin, and levofloxacin in mice. The results showed that the bacterial 16s rRNA expression, luminal concentrations of short-chain fatty acids and bile acids, and plasma glucose levels were significantly lower in ABX-treated mice than in vehicle-treated mice. In addition, ABX treatment significantly reduced renal glucose and pyruvate levels. The mRNA expression levels of glucose-6-phosphatase and phosphoenolpyruvate carboxykinase in the renal cortex were significantly higher in ABX-treated mice than in vehicle-treated mice. We further examined the impact of AIMD on the altered metabolic status in mice after ischemia-induced kidney injury. After exposure to ischemia for 60 min, the renal pyruvate concentrations were significantly lower in ABX-treated mice than in vehicle-treated mice. ABX treatment caused a more severe tubular injury after ischemia-reperfusion (IR). Our findings confirm that AIMD is associated with decreased pyruvate levels in the kidney, which may have been caused by the activation of renal gluconeogenesis. Thus, we hypothesized that AIMD would increase the vulnerability of the kidney to IR injury.

scholarly journals Glucose homeostasis is impaired in mice deficient in the neuropeptide 26RFa (QRFP)

2020 ◽  
Vol 8 (1) ◽  
pp. e000942
Author(s):  
Mouna El-Mehdi ◽  
Saloua Takhlidjt ◽  
Fayrouz Khiar ◽  
Gaëtan Prévost ◽  
Jean-Luc do Rego ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islets ◽  
Glucose Homeostasis ◽  
Gene Knockout ◽  
Hepatic Glucose Production ◽  
Biologically Active ◽  
Mutant Mice ◽  
Insulin Production ◽  
Coding Region ◽  
The Impact

Introduction26RFa (pyroglutamyl RFamide peptide (QRFP)) is a biologically active peptide that has been found to control feeding behavior by stimulating food intake, and to regulate glucose homeostasis by acting as an incretin. The aim of the present study was thus to investigate the impact of 26RFa gene knockout on the regulation of energy and glucose metabolism.Research design and methods26RFa mutant mice were generated by homologous recombination, in which the entire coding region of prepro26RFa was replaced by the iCre sequence. Energy and glucose metabolism was evaluated through measurement of complementary parameters. Morphological and physiological alterations of the pancreatic islets were also investigated.ResultsOur data do not reveal significant alteration of energy metabolism in the 26RFa-deficient mice except the occurrence of an increased basal metabolic rate. By contrast, 26RFa mutant mice exhibited an altered glycemic phenotype with an increased hyperglycemia after a glucose challenge associated with an impaired insulin production, and an elevated hepatic glucose production. Two-dimensional and three-dimensional immunohistochemical experiments indicate that the insulin content of pancreatic β cells is much lower in the 26RFa−/− mice as compared with the wild-type littermates.ConclusionDisruption of the 26RFa gene induces substantial alteration in the regulation of glucose homeostasis, with in particular a deficit in insulin production by the pancreatic islets. These findings further support the notion that 26RFa is an important regulator of glucose homeostasis.

scholarly journals Fecal microbiota transplantation from high caloric-fed donors alters glucose metabolism in recipient mice, independently of adiposity or exercise status

2020 ◽  
Vol 319 (1) ◽  
pp. E203-E216
Author(s):  
Jereon Zoll ◽  
Mark N. Read ◽  
Sarah E. Heywood ◽  
Emma Estevez ◽  
Jessica P. S. Marshall ◽  
...  
Keyword(s):  
Body Composition ◽  
Glucose Metabolism ◽  
Glucose Intolerance ◽  
Fecal Microbiota Transplantation ◽  
High Energy ◽  
Fecal Microbiota ◽  
Metabolic Effects ◽  
Microbiota Composition ◽  
No Donor ◽  
Glucose Levels

Studies suggest the gut microbiota contributes to the development of obesity and metabolic syndrome. Exercise alters microbiota composition and diversity and is protective of these maladies. We tested whether the protective metabolic effects of exercise are mediated through fecal components through assessment of body composition and metabolism in recipients of fecal microbiota transplantation (FMT) from exercise-trained (ET) mice fed normal or high-energy diets. Donor C57BL/6J mice were fed a chow or high-fat, high-sucrose diet (HFHS) for 4 wk to induce obesity and glucose intolerance. Mice were divided into sedentary (Sed) or ET groups (6 wk treadmill-based ET) while maintaining their diets, resulting in four donor groups: chow sedentary (NC-Sed) or ET (NC-ET) and HFHS sedentary (HFHS-Sed) or ET (HFHS-ET). Chow-fed recipient mice were gavaged with feces from the respective donor groups weekly, creating four groups (NC-Sed-R, NC-ET-R, HFHS-Sed-R, HFHS-ET-R), and body composition and metabolism were assessed. The HFHS diet led to glucose intolerance and obesity in the donors, whereas exercise training (ET) restrained adiposity and improved glucose tolerance. No donor group FMT altered recipient body composition. Despite unaltered adiposity, glucose levels were disrupted when challenged in mice receiving feces from HFHS-fed donors, irrespective of donor-ET status, with a decrease in insulin-stimulated glucose clearance into white adipose tissue and large intestine and specific changes in the recipient’s microbiota composition observed. FMT can transmit HFHS-induced disrupted glucose metabolism to recipient mice independently of any change in adiposity. However, the protective metabolic effect of ET on glucose metabolism is not mediated through fecal factors.

scholarly journals Chronic Microvascular Complications in Prediabetic States—An Overview

2020 ◽  
Vol 9 (10) ◽  
pp. 3289
Author(s):  
Angelika Baranowska-Jurkun ◽  
Wojciech Matuszewski ◽  
Elżbieta Bandurska-Stankiewicz
Keyword(s):  
Risk Factor ◽  
Glucose Metabolism ◽  
Microvascular Complications ◽  
Current Data ◽  
Chronic Complications ◽  
Prediabetic State ◽  
Complications Of Diabetes ◽  
Glucose Levels ◽  
Abnormal Glucose Metabolism

A prediabetic state is a major risk factor for the development of diabetes, and, because of an identical pathophysiological background of both conditions, their prevalence increases parallelly and equally fast. Long-term hyperglycemia is the main cause inducing chronic complications of diabetes, yet the range of glucose levels at which they start has not been yet unequivocally determined. The current data show that chronic microvascular complications of diabetes can be observed in patients with abnormal glucose metabolism in whom glycaemia is higher than optimal but below diagnostic criteria for diabetes. Prediabetes is a heterogenous nosological unit in which particular types are differently characterized and show different correlations with particular kinds of complications. Analysis of the latest research results shows the need to continue studies in a larger population and can imply the need to verify the currently employed criteria of diagnosing diabetes and chronic complications of diabetes in people with prediabetes.

scholarly journals Vezatin is required for the maturation of the neuromuscular synapse

2019 ◽  
Vol 30 (20) ◽  
pp. 2571-2583 ◽  
Author(s):  
Natasha Koppel ◽  
Matthew B. Friese ◽  
Helene L. Cardasis ◽  
Thomas A. Neubert ◽  
Steven J. Burden
Keyword(s):  
Mass Spectrometry ◽  
Acetylcholine Receptor ◽  
Transmembrane Protein ◽  
Neuromuscular Synapse ◽  
Mutant Mice ◽  
Initial Formation ◽  
Postnatal Maturation ◽  
Neuromuscular Synapses ◽  
Key Genes

Key genes, such as Agrin, Lrp4, and MuSK, are required for the initial formation, subsequent maturation, and long-term stabilization of mammalian neuromuscular synapses. Additional molecules are thought to function selectively during the evolution and stabilization of these synapses, but these molecular players are largely unknown. Here, we used mass spectrometry to identify vezatin, a two-pass transmembrane protein, as an acetylcholine receptor (AChR)–associated protein, and we provide evidence that vezatin binds directly to AChRs. We show that vezatin is dispensable for the formation of synapses but plays a later role in the emergence of a topologically complex and branched shape of the synapse, as well as the stabilization of AChRs. In addition, neuromuscular synapses in vezatin mutant mice display premature signs of deterioration, normally found only during aging. Thus, vezatin has a selective role in the structural elaboration and postnatal maturation of murine neuromuscular synapses.

scholarly journals PCK1 Deficiency Shortens the Replicative Lifespan of Saccharomyces cerevisiae through Upregulation of PFK1

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Yuan Yuan ◽  
Jia-ying Lin ◽  
Hong-jing Cui ◽  
Wei Zhao ◽  
Hui-ling Zheng ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Glucose Metabolism ◽  
Aging Process ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Critical Role ◽  
Ros Generation ◽  
High Throughput Analysis ◽  
Replicative Lifespan ◽  
Regulatory Pathways ◽  
Glucose Levels

The cytosolic isozyme of phosphoenolpyruvate carboxykinase (PCK1) was the first rate-limiting enzyme in the gluconeogenesis pathway, which exerted a critical role in maintaining the blood glucose levels. PCK1 has been established to be involved in various physiological and pathological processes, including glucose metabolism, lipid metabolism, diabetes, and tumorigenesis. Nonetheless, the association of PCK1 with aging process and the detailed underlying mechanisms of PCK1 on aging are still far to be elucidated. Hence, we herein constructed the PCK1-deficient (pck1Δ) and PCK1 overexpression (PCK1 OE) Saccharomyces cerevisiae. The results unveiled that PCK1 deficiency significantly shortened the replicative lifespan (RLS) in the S. cerevisiae, while overexpression of PCK1 prolonged the RLS. Additionally, we noted that the ROS level was significantly enhanced in PCK1-deficient strain and decreased in PCK1 OE strain. Then, a high throughput analysis by deep sequencing was performed in the pck1Δ and wild-type strains, in an attempt to shed light on the effect of PCK1 on the lifespan of aging process. The data showed that the most downregulated mRNAs were enriched in the regulatory pathways of glucose metabolism. Fascinatingly, among the differentially expressed mRNAs, PFK1 was one of the most upregulated genes, which was involved in the glycolysis process and ROS generation. Thus, we further constructed the pfk1Δpck1Δ strain by deletion of PFK1 in the PCK1-deficient strain. The results unraveled that pfk1Δpck1Δ strain significantly suppressed the ROS level and restored the RLS of pck1Δ strain. Taken together, our data suggested that PCK1 deficiency enhanced the ROS level and shortened the RLS of S. cerevisiae via PFK1.

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