Insulin signaling and glucose transport in insulin resistant human skeletal muscle

Karlsson, Håkan K.R.; Zierath, Juleen R.

doi:10.1007/s12013-007-0030-9

Cited by 121 publications

(90 citation statements)

References 108 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These defects have been proposed to be largely regulated at the level of post-receptor signaling pathways. 29,30 Although the IL-18 resistance reported in this study is an immunological phenomenon, a tempting hypothesis (that remains to be demonstrated) is that a similar resistance to the metabolic effects of IL-18 is also present. Because the low expression of IL-18 receptors on human leukocytes precludes the reliable assessment of the molecules by flow cytometry, we assessed the mRNA expression of IL-18Ra and b by quantitative real-time PCR.…”

Section: Discussionmentioning

confidence: 76%

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

et al. 2008

View full text Add to dashboard Cite

Objective: Interleukin-18 (IL-18) has been recently demonstrated to improve experimental hyperphagia and insulin resistance. Paradoxically, concentrations of circulating IL-18 in obese subjects and in patients with type 2 diabetes are increased. The objective of this study is to provide an explanation for this paradox. Design: We have hypothesized that cells from obese individuals or from patients with type 2 diabetes mellitus have a diminished response to stimulation with IL-18. IL-18 responsiveness was tested by stimulating blood monocytes of obese or diabetes patients with rIL-18 or microbial components. Results: Obese individuals and patients with type 2 diabetes mellitus exhibit increased circulating concentrations of IL-18. More importantly, leukocytes isolated from obese or type 2 diabetes patients respond poorly after stimulation with IL-18, as reflected by defective interferon-g (IFNg) production. The defective response to IL-18 stimulation was accompanied by a 50% reduction in the expression of IL-18R a and b chains. In addition, cells of patients with obesity and diabetes displayed an impaired release of IFNg after challenge with bacterial or fungal pathogens, which was due to defective IL-18-mediated signaling. Conclusion: Patients with obesity or type 2 diabetes mellitus are characterized by lower responses after stimulation with IL-18. This IL-18 resistance explains the association of obesity and diabetes with high IL-18 circulating concentrations, similar to hyperinsulinemia and hyperleptinemia. IL-18 resistance may represent an important mechanism of the increased susceptibility of these patients to a number of infections.

show abstract

Section: Discussionmentioning

confidence: 76%

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This phenomenon includes insulin-independent [12] and insulindependent glucose clearance [14] as has been demonstrated in humans at risk of diabetes. Insulin action is not solely restricted to GLUTs regulation, but also to glucose homeostasis through hepatic glucose production suppression and stimulation of peripheral combustion [15].…”

Section: General Overview Of Type 2-diabetes Mellitus (T2dm)mentioning

confidence: 80%

“…GLUTs mediate insulin-stimulated glucose uptake in these organs and tissues by a mechanism involving translocation between cellular compartments. GLUT isoforms expression is regulated by insulin and other factors such as hypoxemia, oxidative phosphorylation and osmotic stresses [12].…”

Section: General Overview Of Type 2-diabetes Mellitus (T2dm)mentioning

confidence: 99%

“…Insulin action signal transduction is impaired in skeletal muscle from T2DM subjects underscoring the contribution of molecular defects underlying the insulin resistant phenotype [12]. The fact that this process has been observed in cultured myoblasts after several passages suggests a genetic origin in connection with a heightened state of oxidative stress [17].…”

Section: General Overview Of Type 2-diabetes Mellitus (T2dm)mentioning

confidence: 99%

See 1 more Smart Citation

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

Guillen-Nieto¹,

Herrera-Martínez²

2013

J Diabetes Metab

View full text Add to dashboard Cite

T2DM is a heterogeneous group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Hyperglycemia may simply represent the tip of a broad series of molecular events from mitochondrial damages, to epigenetic and metabolic pathways deregulations. At the same time, hyperglycemia appears as the most proximal trigger for the onset and perpetual progression of multi-organ complications even under normoglycemic conditions. Thus, the initial hyperglycemic hit translates into a permanently harmful cellular imprinting as has been demonstrated in diabetic donors' cells after several passages and cultured in ideal conditions. The wound healing failure along with the inability of the innate immunity to control peripheral infections is the hybrid that determines that 85% of all non-traumatic lower extremity amputations are practiced in diabetic subjects. Diabetic wounds exhibit a complex networking of inflammatory cytokines, local proteases, cytotoxic reactive oxygen and nitrogen species and a polymicrobial biofilm that impose a stagnant phenotype. All these ingredients negatively impact on fibroblasts, endothelial cells and keratinocytes while paradoxically perpetuate the immuno-inflammatory infiltrate. Although the molecular fundamentals toward chronification have not been elucidated, it seems that different gene simultaneously converge to impose the wound cells a pro-senescent, pro-catabolic and pro-apoptotic phenotype given the lack of a "physiological tuning" of tyrosine kinase-dependent receptors due to their limited activation by insulin and local growth factors. Although recombinant growth factors and smart devices have been introduced during the last years the figures of amputations are still discouraging. Faults have been committed while selecting the appropriate growth factor and because of the "chronic" instinct to treat the chronic wounds topically, where bioavailability of the active principle is compromised by wound and bacterial biofilm proteases. The periodic intralesional infiltration of epidermal growth factor has proved to overcome this hurdle. Granulation tissue growth stimulation and wound healing capacity has been restored in diabetic patients by this procedure in several clinical trials and common clinical practice studies.

show abstract

“…In insulin resistant states, such as type 2 diabetes and obesity, insulin stimulated glucose disposal in skeletal muscle is markedly impaired [22][23][24][25][26][27][28]. The decreased insulin-stimulated glucose uptake is due to impaired insulin signaling, and multiple post receptor intracellular defects, including impaired glucose transport and glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis [29][30][31][32].…”

Section: Skeletal Muscle Insulin Resistancementioning

confidence: 99%

The Prevention and Treatment of Type 2 Diabetes Mellitus with a Plant-Based Diet

Strombom¹,

Rose²

2017

EMIJ

View full text Add to dashboard Cite

Those following a plant-based diet have a 78% reduction risk of Type II diabetes mellitus (T2DM), as well as a 56% reduced risk of metabolic syndrome and a lower average BMI, 22.4 for men and 21.8 for women. Vegetarians have less skeletal intramyocellular lipids, and better myocellular glucose disposal and mitochondrial function, and therefore have less peripheral insulin resistance. Vegetarians and vegans also have a much better inflammatory status, indicated by lower levels of inflammatory markers such as CRP and inflammatory adipocytokines such as IL-6, leptin, and higher levels of anti-inflammatory adipocytokines such as adiponectin. Those following a plant-based diet consume much less persistent organic pollutants (POPs) which have been shown to cause beta-cell mitochondrial dysfunction. Finally, the gut microbiome of vegetarians has been shown to play a role in reducing insulin resistance and the level of inflammation in the body, and consequently their risk of T2DM. Interventional studies show a reduction of HbA1C by as much as 2.4 percentage pts, which is more than is usually achieved with Metformin. Other clinical variables also show improvement such as reductions in BMI, total and LDL cholesterol and hsCRP. Studies show compliance rates are good, ranging from 84% to 99%. Medications should be titrated as the patient shows improvements. Treatment with a plantbased diet has no contraindications or adverse reactions. Keywords:

show abstract

Insulin signaling and glucose transport in insulin resistant human skeletal muscle

Cited by 121 publications

References 108 publications

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Interleukin-18 resistance in patients with obesity and type 2 diabetes mellitus

Type 2 Diabetes Mellitus (T2DM): Biological Overview from Pathways to Organelles and its Translation toward a Torpid Wound Healing Process

The Prevention and Treatment of Type 2 Diabetes Mellitus with a Plant-Based Diet

Contact Info

Product

Resources

About