Anti-diabetes effect of chronic intermittent hypobaric hypoxia through improving liver insulin resistance in diabetic rats

Tian, Yanming; Liu, Yan; Wang, Sheng; Dong, Yanbo; Su, Tong; Ma, Huijie; Zhang, Yi

doi:10.1016/j.lfs.2016.02.053

Cited by 33 publications

(20 citation statements)

References 38 publications

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“…The question is still open and it would be of interest to assess different magnitudes and frequencies of IH, as recent literature suggests that the IH-related consequences can be rather different and even beneficial depending on the severity of the hypoxic stimulus 36 . Whereas some studies reported beneficial effects of chronic hypobaric hypoxia (that mimics high altitude exposure) on glucose regulation 37 , 38 , others demonstrated that both sustained and intermittent hypoxia impairs glucose regulation 16 , 39 , with a more deleterious impact of IH on HOMA index 39 , oxidative stress and adipose tissue inflammation 16 . Finally, besides the IH stimulus, the subject vulnerability (i.e.…”

Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia-induced insulin resistance is associated with alterations in white fat distribution

Poulain

Mathieu

Thomas

et al. 2017

Sci Rep

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Sleep apnea syndrome is characterized by repetitive upper airway collapses during night leading to intermittent hypoxia (IH). The latter is responsible for metabolic disturbances that rely, at least in part, on abdominal white fat inflammation. Besides qualitative alterations, we hypothesized that IH could also modify body fat distribution, a key factor for metabolic complications. C57BL6 mice exposed to IH (21–5% FiO2, 60 s cycle, 8 h/day) or air for 6 weeks were investigated for topographic fat alterations (whole-body MRI). Specific role of epididymal fat in IH-induced metabolic dysfunctions was assessed in lipectomized or sham-operated mice exposed to IH or air. Whereas total white fat volume was unchanged, IH induced epididymal adipose tissue (AT) loss with non-significant increase in subcutaneous and mesenteric fat. This was associated with impaired insulin sensitivity and secretion. Epididymal lipectomy led to increased subcutaneous fat in the perineal compartment and prevented IH-induced metabolic disturbances. IH led to reduced epididymal AT and impaired glucose regulation. This suggests that, rather than epididymal AT volume, qualitative fat alterations (i.e. inflammation) could represent the main determinant of metabolic dysfunction. This deterioration of glucose regulation was prevented in epididymal-lipectomized mice, possibly through prevention of IH-induced epididymal AT alterations and compensatory increase in subcutaneous AT.

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Section: Discussionmentioning

confidence: 99%

Intermittent hypoxia-induced insulin resistance is associated with alterations in white fat distribution

Poulain

Mathieu

Thomas

et al. 2017

Sci Rep

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“…11,12 In particular, it was shown that hypoxic training increased glycolytic enzyme activities, enhanced the number of mitochondria in skeletal muscles, and improved insulin sensitivity as well. 13,14 Glucose-lowering effects of IHT were also previously reported in diabetic patients 15,16 and the beneficial effect is particularly important in elderly population with higher risks in developing diabetes.…”

Section: Introductionmentioning

confidence: 75%

Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression

Serebrovskaya

Portnychenko

Drevytska

et al. 2017

Exp Biol Med (Maywood)

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The present study investigated the beneficial effects of intermittent hypoxia training (IHT) in humans under prediabetic conditions. We found that three-week moderate IHT induced higher HIF-1a mRNA expressions as well as its target genes, which were positively correlated with higher tolerance to acute hypoxia and better glucose homeostasis in both middle-aged healthy and prediabetic subjects. This small clinical trial has provided new data suggesting a potential utility of IHT for management of prediabetes patients. AbstractThe present study aimed at examining beneficial effects of intermittent hypoxia training (IHT) under prediabetic conditions. We investigate the effects of three-week IHT on blood glucose level, tolerance to acute hypoxia, and leukocyte mRNA expression of hypoxia inducible factor 1a (HIF-1a) and its target genes, i.e. insulin receptor, facilitated glucose transporter-solute carrier family-2, and potassium voltage-gated channel subfamily J. Seven healthy and 11 prediabetic men and women (44-70 years of age) were examined before, next day and one month after three-week IHT (3 sessions per week, each session consisting 4 cycles of 5-min 12% O 2 and 5-min room air breathing). We found that IHT afforded beneficial effects on glucose homeostasis in patients with prediabetes reducing fasting glucose and during standard oral glucose tolerance test. The most pronounced positive effects were observed at one month after IHT termination. IHT also significantly increased the tolerance to acute hypoxia (i.e. SaO 2 level at 20th min of breathing with 12% O 2 ) and improved functional parameters of respiratory and cardiovascular systems. IHT stimulated HIF-1a mRNA expression in blood leukocytes in healthy and prediabetic subjects, but in prediabetes patients the maximum increase was lagged. The greatest changes in mRNA expression of HIF-1a target genes occurred a month after IHT and coincided with the largest decrease in blood glucose levels. The higher expression of HIF-1a was positively associated with higher tolerance to hypoxia and better glucose homeostasis. In conclusion, our results suggest that IHT may be useful for preventing the development of type 2 diabetes.

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“…Chronic intermittent hypobaric hypoxia (CIHH) is a treatment with moderate hypoxia simulating high altitude interrupted by normoxia. Many studies have shown that CIHH has numerous beneficial effects, such as cardiac protection 8 , anti-hypertension 9 , anti-inflammation and modulation of immune function 10 , 11 , and adjustment of metabolic dysfunctions 12 , 13 . Our previous studies have demonstrated that CIHH promotes the recovery of cardiac function, diminishes infarction area, and antagonizes arrhythmia induced by ischemia/reperfusion (I/R) 8 , 14 .…”

Section: Introductionmentioning

confidence: 99%

Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress

Fang

Zhang

et al. 2017

Sci Rep

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We investigated the role of endoplasmic reticulum stress (ERS) in chronic intermittent hypobaric hypoxia (CIHH)-induced cardiac protection. Adult male Sprague-Dawley rats were exposed to CIHH treatment simulating 5000 m altitude for 28 days, 6 hours per day. The heart was isolated and perfused with Langendorff apparatus and subjected to 30-min ischemia followed by 60-min reperfusion. Cardiac function, infarct size, and lactate dehydrogenase (LDH) activity were assessed. Expression of ERS molecular chaperones (GRP78, CHOP and caspase-12) was assayed by western blot analysis. CIHH treatment improved the recovery of left ventricular function and decreased cardiac infarct size and activity of LDH after I/R compared to control rats. Furthermore, CIHH treatment inhibited over-expression of ERS-related factors including GRP78, CHOP and caspase-12. CIHH-induced cardioprotection and inhibition of ERS were eliminated by application of dithiothreitol, an ERS inducer, and chelerythrine, a protein kinase C (PKC) inhibitor. In conclusion CIHH treatment exerts cardiac protection against I/R injury through inhibition of ERS via PKC signaling pathway.

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Anti-diabetes effect of chronic intermittent hypobaric hypoxia through improving liver insulin resistance in diabetic rats

Cited by 33 publications

References 38 publications

Intermittent hypoxia-induced insulin resistance is associated with alterations in white fat distribution

Intermittent hypoxia-induced insulin resistance is associated with alterations in white fat distribution

Intermittent hypoxia training in prediabetes patients: Beneficial effects on glucose homeostasis, hypoxia tolerance and gene expression

Chronic Intermittent Hypobaric Hypoxia Improves Cardiac Function through Inhibition of Endoplasmic Reticulum Stress

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