Mitochondrial dysfunction and insulin resistance: an update

Montgomery, Magdalene K; Turner, Nigel

doi:10.1530/ec-14-0092

Cited by 408 publications

(327 citation statements)

References 136 publications

(110 reference statements)

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“…But more insulin sensitive cells are in the adipocytes, muscle and hepatocytes. So, circulating insulin in the bloodstream is captured by alpha subunits (glycine 1-154) and both of them form a whole to incorporate the D-glucose in the cell of manner indirect through the glucose transporters (GLUTs) [104][105][106][107][108][109] and after this, the insulin receptor can be desintegrated or return to the cellular surface [97,100,105].…”

Section: Insulin Receptormentioning

confidence: 99%

Therapeutic Methods Against Insulin Resistance

Rafael¹

2016

J Endocrinol Metab

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Clinical, neurosurgical and autopsy findings show that type 2 diabetes mellitus is caused by progressive ischemia in the anterior hypothalamus and endocrine pancreas due to atherosclerosis, and associated with insulin resistance. The hypothalamic ischemia provokes neuroendocrinological disorders through descending projections, and the pancreatic ischemia causes an inappropriate insulin secretion. Both ischemic structures can be improved by means of omental implantation (omental transplantation or transposition) or with anti-inflammatory drugs. Likewise, experimental and clinical observations suggest that insulin resistance is caused by inflammatory action of tumor necrosis factor alpha and resistin in the insulin receptor. Because, in contrast to this, high-dose aspirin or resveratrol can reduce hyperglycemia to normal or near normal in diabetic patients. That is, both drugs are almost specific for the treatment of insulin resistance. Finally, the use of clonazepam at night can have a beneficial effect on glucose homeostasis, because it can reduce the effects of stressful stimuli and normalize the sleep disorders or loss.

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Section: Insulin Receptormentioning

confidence: 99%

Therapeutic Methods Against Insulin Resistance

Rafael¹

2016

J Endocrinol Metab

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“…Impaired insulin signaling has been associated with mitochondrial dysfunction in diabetes mellitus and cardiac disorders 4, 28. However, it remains a matter of debate whether mitochondrial dysfunction results in insulin resistance or vice versa 29, 30.…”

Section: Discussionmentioning

confidence: 99%

“…In diabetes mellitus, mitochondrial dysfunction has been associated with insulin resistance. Studies have shown that impaired mitochondrial function may cause insulin resistance in skeletal muscle 4. Notably, the reverse relationship may also exist, which applies particularly to the heart.…”

mentioning

confidence: 99%

Increased Protein Tyrosine Phosphatase 1B (PTP1B) Activity and Cardiac Insulin Resistance Precede Mitochondrial and Contractile Dysfunction in Pressure‐Overloaded Hearts

Nguyễn

Schwarzer

Schrepper

et al. 2018

JAHA

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BackgroundInsulin resistance in diabetes mellitus has been associated with mitochondrial dysfunction. Defects at the level of mitochondria are also characteristic of heart failure. We assessed changes in cardiac insulin response and mitochondrial function in a model of pressure overload‐induced heart failure.Methods and ResultsRats underwent aortic banding to induce pressure overload. At 10 weeks, rats showed cardiac hypertrophy and pulmonary congestion, but left ventricular dilatation and systolic dysfunction were only evident after 20 weeks. This contractile impairment was accompanied by mitochondrial dysfunction as shown by markedly reduced state 3 respiration of isolated mitochondria. Aortic banding did not affect systemic insulin response. However, insulin‐stimulated cardiac glucose uptake and glucose oxidation were significantly diminished at 10 and 20 weeks, which indicates cardiac insulin resistance starting before the onset of mitochondrial and contractile dysfunction. The impaired cardiac insulin action was related to a decrease in insulin‐stimulated phosphorylation of insulin receptor β. Consistently, we found elevated activity of protein tyrosine phosphatase 1B (PTP1B) at 10 and 20 weeks, which may blunt insulin action by dephosphorylating insulin receptor β. PTP1B activity was also significantly increased in left ventricular samples of patients with systolic dysfunction undergoing aortic valve replacement because of aortic stenosis.ConclusionsPressure overload causes cardiac insulin resistance that precedes and accompanies mitochondrial and systolic dysfunction. Activation of PTP1B in the heart is associated with heart failure in both rats and humans and may account for cardiac insulin resistance. PTP1B may be a potential target to modulate insulin sensitivity and contractile function in the failing heart.

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“…Mitochondrial dysfunction has been implicated in the development of insulin resistance, but it is still unclear if there is a causal relationship (Montgomery and Turner 2015), and recently it has been suggested that rather an increase in mitochondrial efficiency precedes the development of insulin resistance as shown in a rat model of high-fat diet feeding (Crescenzo et al 2014). It is interesting to note that an uncoupling induced decrease in mitochondrial efficiency (Neschen et al 2008) in turn leads to a protection from diabetes development.…”

Section: Discussionmentioning

confidence: 99%

Skeletal muscle mitochondrial uncoupling prevents diabetes but not obesity in NZO mice, a model for polygenic diabesity

et al. 2015

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Induction of skeletal muscle (SM) mitochondrial stress by expression of uncoupling protein 1 (UCP1) in mice results in a healthy metabolic phenotype associated with increased secretion of FGF21 from SM. Here, we investigated whether SM mitochondrial uncoupling can compensate obesity and insulin resistance in the NZO mouse, a polygenic diabesity model. Male NZO mice were crossed with heterozygous UCP1 transgenic (tg) mice (mixed C57BL/6/CBA background) and further backcrossed to obtain F1 and N2 offspring with 50 and 75 % NZO background, respectively. Male F1 and N2 progeny were fed a high-fat diet ad libitum for 20 weeks from weaning. Blood glucose was reduced, and diabetes (severe hyperglycemia [300 mg/dl) was fully prevented in both F1-and N2-tg progeny compared to a diabetes prevalence of 15 % in F1 and 42 % in N2 wild type. In contrast, relative body fat content and plasma insulin were decreased, and glucose tolerance was improved, in F1-tg only. Both F1 and N2-tg showed decreased lean body mass. Accordingly, induction of SM stress response including FGF21 expression and secretion was similar in both F1 and N2-tg mice. In white adipose tissue, expression of FGF21 target genes was enhanced in F1 and N2-tg mice, whereas lipid metabolism genes were induced in F1-tg only. There was no evidence for induction of browning in either UCP1 backcross. We conclude that SM mitochondrial uncoupling induces FGF21 expression and prevents diabetes in mice with a 50-75 % NZO background independent of its effects on adipose tissue.

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Mitochondrial dysfunction and insulin resistance: an update

Cited by 408 publications

References 136 publications

Therapeutic Methods Against Insulin Resistance

Therapeutic Methods Against Insulin Resistance

Increased Protein Tyrosine Phosphatase 1B (PTP1B) Activity and Cardiac Insulin Resistance Precede Mitochondrial and Contractile Dysfunction in Pressure‐Overloaded Hearts

Skeletal muscle mitochondrial uncoupling prevents diabetes but not obesity in NZO mice, a model for polygenic diabesity

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