Effects of Dietary Restriction on the Expression of Insulin-Signaling-Related Genes in Long-Lived Mutant Mice

2006 ◽  
pp. 69-82 ◽  
Author(s):  
Andrzej Bartke ◽  
Michal M. Masternak ◽  
Khalid A. Al-Regaiey ◽  
Michael S. Bonkowski
Keyword(s):  
Dietary Restriction ◽  
Insulin Signaling ◽  
Mutant Mice

scholarly journals Pulmonary vascular effect of insulin in a rodent model of pulmonary arterial hypertension

2017 ◽  
Vol 7 (3) ◽  
pp. 624-634 ◽  
Author(s):  
Aaron W. Trammell ◽  
Megha Talati ◽  
Thomas R. Blackwell ◽  
Niki L. Fortune ◽  
Kevin D. Niswender ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Endothelial Cells ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Glucose Uptake ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Western Diet ◽  
Mutant Mice ◽  
Pulmonary Arterial

Pulmonary arterial hypertension (PAH) is associated with metabolic derangements including insulin resistance, although their effects on the cardiopulmonary disease are unclear. We hypothesized that insulin resistance promotes pulmonary hypertension (PH) development and mutations in type 2 bone morphogenetic protein receptor (BMPR2) cause cellular insulin resistance. Using a BMPR2 transgenic murine model of PAH and two models of inducible diabetes mellitus, we explored the impact of hyperglycemia and/or hyperinsulinemia on development and severity of PH. We assessed insulin signaling and insulin-mediated glucose uptake in human endothelial cells with and without mutations in BMPR2. PH developed in control mice fed a Western diet and PH in BMPR2 mutant mice was increased by Western diet. Pulmonary artery pressure correlated strongly with fasting plasma insulin but not glucose. Reactive oxygen species were increased in lungs of insulin-resistant animals. BMPR2 mutation impaired insulin-mediated endothelial glucose uptake via reduced glucose transporter translocation despite intact insulin signaling. Experimental hyperinsulinemia is strongly associated with PH in both control and BMPR2-mutant mice, though to a greater degree in those with BMPR2 mutation. Human pulmonary endothelial cells with BMPR2 mutation have evidence of reduced glucose uptake due to impaired glucose transporter translocation. These experiments support a role for hyperinsulinemia in pulmonary vascular disease.

scholarly journals Insulin Signaling and Dietary Restriction Differentially Influence the Decline of Learning and Memory with Age

PLoS Biology ◽  
2010 ◽  
Vol 8 (5) ◽  
pp. e1000372 ◽  
Author(s):  
Amanda L. Kauffman ◽  
Jasmine M. Ashraf ◽  
M. Ryan Corces-Zimmerman ◽  
Jessica N. Landis ◽  
Coleen T. Murphy
Keyword(s):  
Learning And Memory ◽  
Dietary Restriction ◽  
Insulin Signaling

Insulin secretion and signaling in response to dietary restriction and subsequent re-alimentation in cattle

2015 ◽  
Vol 47 (8) ◽  
pp. 344-354 ◽  
Author(s):  
Kate Keogh ◽  
David A. Kenny ◽  
Alan K. Kelly ◽  
Sinéad M. Waters
Keyword(s):  
Skeletal Muscle ◽  
Signaling Pathway ◽  
Dietary Restriction ◽  
Insulin Signaling ◽  
Compensatory Growth ◽  
Insulin Response ◽  
Insulin Signaling Pathway ◽  
Longissimus Dorsi ◽  
Period 2 ◽  
Ad Libitum

The objectives of this study were to examine systemic insulin response to a glucose tolerance test (GTT) and transcript abundance of genes of the insulin signaling pathway in skeletal muscle, during both dietary restriction and re-alimentation-induced compensatory growth. Holstein Friesian bulls were blocked to one of two groups: 1) restricted feed allowance for 125 days ( period 1) (RES, n = 15) followed by ad libitum feeding for 55 days ( period 2) or 2) ad libitum access to feed throughout (periods 1 and 2) (ADLIB, n = 15). On days 90 and 36 of periods 1 and 2, respectively, a GTT was performed. M. longissimus dorsi biopsies were harvested from all bulls on days 120 and 15 of periods 1 and 2, respectively, and RNA-Seq analysis was performed. RES displayed a lower growth rate during period 1 (RES: 0.6 kg/day, ADLIB: 1.9 kg/day; P < 0.001), subsequently gaining more during re-alimentation (RES: 2.5 kg/day, ADLIB: 1.4 kg/day; P < 0.001). Systemic insulin response to glucose administration was lower in RES in period 1 ( P < 0.001) with no difference observed during period 2. The insulin signaling pathway in M. longissimus dorsi was enriched ( P < 0.05) in response to dietary restriction but not during re-alimentation ( P > 0.05). Genes differentially expressed in the insulin signaling pathway suggested a greater sensitivity to insulin in skeletal muscle, with pleiotropic effects of insulin signaling interrupted during dietary restriction. Collectively, these results indicate increased sensitivity to glucose clearance and skeletal muscle insulin signaling during dietary restriction; however, no overall role for insulin was apparent in expressing compensatory growth.

scholarly journals Lifespan and Glucose Metabolism in Insulin Receptor Mutant Mice

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Takahiko Shimizu ◽  
Tomonori Baba ◽  
Midori Ogawara ◽  
Takuji Shirasawa
Keyword(s):  
Oxidative Stress ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Biological Significance ◽  
Mutant Mice ◽  
Male Mice ◽  
Wild Type ◽  
Female Mice ◽  
Mutant Female ◽  
Mutant Male

Insulin/insulin-like growth factor type 1 signaling regulates lifespan and resistance to oxidative stress in worms, flies, and mammals. In a previous study, we revealed that insulin receptor (IR) mutant mice, which carry a homologous mutation found in the long-liveddaf-2 mutant ofCaenorhabditis elegans, showed enhanced resistance to oxidative stress cooperatively modulated by sex hormones and dietary signals (Baba et al., (2005)). We herein investigated the lifespan of IR mutant mice to evaluate the biological significance of insulin signaling in mice. Under normoxia, mutant male mice had a lifespan comparable to that of wild-type male mice. IR mutant female mice also showed a lifespan similar to that of wild-type female mice, in spite of the fact that the IR mutant female mice acquired more resistance to oxidative stress than IR mutant male mice. On the other hand, IR mutant male and female mice both showed insulin resistance with hyperinsulinemia, but they did not develop hyperglycemia throughout their entire lifespan. These data indicate that the IR mutation does not impact the lifespan in mice, thus suggesting that insulin signaling might have a limited effect on the lifespan of mice.

scholarly journals Estrogen, Insulin, and Dietary Signals Cooperatively Regulate Longevity Signals to Enhance Resistance to Oxidative Stress in Mice

2005 ◽  
Vol 280 (16) ◽  
pp. 16417-16426 ◽  
Author(s):  
Tomonori Baba ◽  
Takahiko Shimizu ◽  
Yo-ichi Suzuki ◽  
Midori Ogawara ◽  
Kyo-ichi Isono ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Receptor ◽  
Insulin Signaling ◽  
Manganese Superoxide Dismutase ◽  
Biological Significance ◽  
Mutant Mice ◽  
Male Mice ◽  
Wild Type ◽  
Female Mice ◽  
Wild Type Female

To investigate the biological significance of a longevity mutation found indaf-2 ofCaenorhabditis elegans, we generated a homologous murine model by replacing Pro-1195 of insulin receptors with Leu using a targeted knock-in strategy. Homozygous mice died in the neonatal stage from diabetic ketoacidosis, whereas heterozygous mice showed the suppressed kinase activity of the insulin receptor but grew normally without spontaneously developing diabetes during adulthood. We examined heterozygous insulin receptor mutant mice for longevity phenotypes. Under 80% oxygen, mutant female mice survived 33.3% longer than wild-type female mice, whereas mutant male mice survived 18.2% longer than wild-type male mice. These results suggested that mutant mice acquired more resistance to oxidative stress, but the benefit of the longevity mutation was more pronounced in females than males. Manganese superoxide dismutase activity in mutant mice was significantly upregulated, suggesting that the suppressed insulin signaling leads to an enhanced antioxidant defense. To analyze the molecular basis of the gender difference, we administered estrogen to mutant mice. It was found that the survival of mice under 80% oxygen was extended when they were administered estradiol. In contrast, mutant and wild-type female mice showed shortened survivals when their ovaries were removed. The influence of estrogen is remarkable in mutant mice compared with wild-type mice, suggesting that estrogen modulates insulin signaling in mutant mice. Furthermore, we showed additional extension of survival under oxidative conditions when their diet was restricted. Collectively, we show that three distinct signals; insulin, estrogen, and dietary signals work in independent and cooperative ways to enhance the resistance to oxidative stress in mice.

New insights into heparan sulphate biosynthesis from the study of mutant mice

2002 ◽  
Vol 69 ◽  
pp. 47-57 ◽  
Author(s):  
Catherine L. R. Merry ◽  
John T. Gallagher
Keyword(s):  
Growth Factors ◽  
Biosynthetic Pathway ◽  
Heparan Sulphate ◽  
Mutant Mice ◽  
Gene Products ◽  
Multiple Gene ◽  
Adhesion Proteins ◽  
Ligand Interactions

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.

Author response for "Protection from EAE in DOCK8 mutant mice occurs despite increased Th17 cell frequencies in the periphery"

2018 ◽  
Author(s):  
Alicia S. Wilson ◽  
Hsei Di Law ◽  
Christiane B. Knobbe‐Thomsen ◽  
Conor J. Kearney ◽  
Jane Oliaro ◽  
...  
Keyword(s):  
Th17 Cell ◽  
Mutant Mice ◽  
Author Response
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