scholarly journals Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging

F1000Research ◽  
2015 ◽  
Vol 3 ◽  
pp. 256
Author(s):  
Oge Arum ◽  
Jamal Saleh ◽  
Ravneet Boparai ◽  
Jeremy Turner ◽  
John Kopchick ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Caloric Restriction ◽  
Gene Disruption ◽  
Growth Hormone Receptor ◽  
Protein Gene ◽  
Binding Protein Gene ◽  
Ad Libitum ◽  
Insulin Responsiveness ◽  
Glycemic Regulation ◽  
Receptor Binding Protein

The correlation of physiological sensitivity to insulin (vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice.

scholarly journals Interaction of growth hormone receptor/binding protein gene disruption and caloric restriction for insulin sensitivity and attenuated aging

F1000Research ◽  
2014 ◽  
Vol 3 ◽  
pp. 256 ◽  
Author(s):  
Oge Arum ◽  
Jamal Saleh ◽  
Ravneet Boparai ◽  
Jeremy Turner ◽  
John Kopchick ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Caloric Restriction ◽  
Gene Disruption ◽  
Growth Hormone Receptor ◽  
Protein Gene ◽  
Binding Protein Gene ◽  
Ad Libitum ◽  
Insulin Responsiveness ◽  
Glycemic Regulation ◽  
Receptor Binding Protein

The correlation of physiological sensitivity to insulin (vis-à-vis glycemic regulation) and longevity is extensively established, creating a justifiable gerontological interest on whether insulin sensitivity is causative, or even predictive, of some or all phenotypes of slowed senescence (including longevity). The growth hormone receptor/ binding protein gene-disrupted (GHR-KO) mouse is the most extensively investigated insulin-sensitive, attenuated aging model. It was reported that, in a manner divergent from similar mutants, GHR-KO mice fail to respond to caloric restriction (CR) by altering their insulin sensitivity. We hypothesized that maximized insulin responsiveness is what causes GHR-KO mice to exhibit a suppressed survivorship response to dietary (including caloric) restriction; and attempted to refute this hypothesis by assessing the effects of CR on GHR-KO mice for varied slow-aging-associated phenotypes. In contrast to previous reports, we found GHR-KO mice on CR to be less responsive than their ad libitum (A.L.) counterparts to the hypoglycemia-inducing effects of insulin. Further, CR had negligible effects on the metabolism or cognition of GHR-KO mice. Therefore, our data suggest that the effects of CR on the insulin sensitivity of GHR-KO mice do not concur with the effects of CR on the aging of GHR-KO mice.

scholarly journals Protection against Diabetes-Induced Nephropathy in Growth Hormone Receptor/Binding Protein Gene-Disrupted Mice1

Endocrinology ◽  
2000 ◽  
Vol 141 (1) ◽  
pp. 163-168 ◽  
Author(s):  
Linda L. Bellush ◽  
Sophie Doublier ◽  
Amy N. Holland ◽  
Liliane J. Striker ◽  
Gary E. Striker ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Receptor Binding ◽  
Hormone Receptor ◽  
Growth Hormone Receptor ◽  
Protein Gene ◽  
Binding Protein ◽  
Binding Protein Gene ◽  
Receptor Binding Protein

scholarly journals Knockdown of angiopoietin-like 2 mimics the benefits of intermittent fasting on insulin responsiveness and weight loss

2017 ◽  
Vol 243 (1) ◽  
pp. 45-49 ◽  
Author(s):  
Cécile Martel ◽  
Anthony Pinçon ◽  
Alexandre Maxime Bélanger ◽  
Xiaoyan Luo ◽  
Marc-Antoine Gillis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Intake ◽  
Intermittent Fasting ◽  
Wild Type ◽  
Beneficial Effects ◽  
Obesity And Diabetes ◽  
Ad Libitum ◽  
Insulin Responsiveness

Angiopoietin-like 2 (ANGPTL2) is an inflammatory adipokine linking obesity to insulin resistance. Intermittent fasting, on the other hand, is a lifestyle intervention able to prevent obesity and diabetes but difficult to implement and maintain. Our objectives were to characterize a link between ANGPTL2 and intermittent fasting and to investigate whether the knockdown of ANGPTL2 reproduces the benefits of intermittent fasting on weight gain and insulin responsiveness in knockdown and wild-type littermates mice. Intermittent fasting, access to food ad libitum once every other day, was initiated at the age of three months and maintained for four months. Intermittent fasting decreased by 63% (p < 0.05) gene expression of angptl2 in adipose tissue of wild-type mice. As expected, intermittent fasting improved insulin sensitivity (p < 0.05) and limited weight gain (p < 0.05) in wild-type mice. Knockdown mice fed ad libitum, however, were comparable to wild-type mice following the intermittent fasting regimen: insulin sensitivity and weight gain were identical, while intermittent fasting had no additional impact on these parameters in knockdown mice. Energy intake was similar between both wild-type fed intermittent fasting and ANGPTL2 knockdown mice fed ad libitum, suggesting that intermittent fasting and knockdown of ANGPTL2 equally lower feeding efficiency. These results suggest that the reduction of ANGPTL2 could be a useful and promising strategy to prevent obesity and insulin resistance, although further investigation of the mechanisms linking ANGPTL2 and intermittent fasting is warranted. Impact statement Intermittent fasting is an efficient diet pattern to prevent weight gain and improve insulin sensitivity. It is, however, a difficult regimen to follow and compliance is expected to be very low. In this work, we demonstrate that knockdown of ANGPTL2 in mice fed ad libitum mimics the beneficial effects of intermittent fasting on weight gain and insulin sensitivity in wild-type mice. ANGPTL2 is a cytokine positively associated with fat mass in humans, which inactivation in mice improves resistance to a high-fat metabolic challenge. This study provides a novel pathway by which IF acts to limit obesity despite equivalent energy intake. The development of a pharmacological ANGPTL2 antagonist could provide an efficient tool to reduce the burden of obesity.

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