Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet

Broussard, Josiane L.; Bergman, Richard N.; Bediako, Isaac Asare; Paszkiewicz, Rebecca L.; Iyer, Malini S.; Kolka, Cathryn M.

doi:10.1002/oby.22057

Cited by 7 publications

(13 citation statements)

References 31 publications

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“…Unravelling the mechanism of insulin interaction with microvascular endothelial cells is paramount, as insulin delivery to tissues (e.g., muscle) is compromised in obesity and during saturated fat intake (9).…”

Section: Introductionmentioning

confidence: 99%

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Jaldín-Fincati

Pereira

Bilan

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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Whereas the blood microvasculature constitutes a biological barrier to the action of blood-borne insulin on target tissues, the lymphatic microvasculature might act as a barrier to subcutaneously administrated insulin reaching the circulation. Here, we evaluate the interaction of insulin with primary microvascular endothelial cells of lymphatic [human dermal lymphatic endothelial cells (HDLEC)] and blood [human adipose microvascular endothelial cells (HAMEC)] origin, derived from human dermal and adipose tissues, respectively. HDLEC express higher levels of insulin receptor and signal in response to insulin as low as 2.5 nM, while HAMEC only activate signaling at 100 nM (a dose that blood vessels do not normally encounter). Low insulin acts specifically through the insulin receptor, while supraphysiological insulin acts through both the IR and insulin growth factor-1 receptor. At supraphysiological or injection site-compatible doses pertinent to lymphatic microvessels, insulin enters HAMEC and HDLEC via fluid-phase endocytosis. Conversely, at physiologically circulating doses (0.2 nM) pertinent to blood microvessels, insulin enters HAMEC through a receptor-mediated process requiring IR autophosphorylation but not downstream insulin signaling. At physiological doses, internalized insulin is barely degraded and is instead released intact to the extracellular medium. In conclusion, we document for the first time the mechanism of interaction of insulin with lymphatic endothelial cells, which may be relevant to insulin absorption during therapeutic injections. Furthermore, we describe distinct action and uptake routes for insulin at physiological and supraphysiological doses in blood microvascular endothelial cells, providing a potential explanation for previously conflicting studies on endothelial insulin uptake.

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Section: Introductionmentioning

confidence: 99%

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Jaldín-Fincati

Pereira

Bilan

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

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“…In comparison, as there is no insulin resistance to compensate for, the PUFA diet does not alter insulin clearance, and may even reduce insulin release. 67 These results on hyperinsulinaemia occur in response to insulin resistance, but without effect on plasma glucose levels, which suggests that hyperinsulinaemia develops in response to insulin resistance. However, it has been assumed that hyperglycaemia is the cause of disease: with this dogma, many therapies targeting diabetes treatment aim to lower glucose, without regard to insulin levels.…”

Section: S K Ele Tal Musclementioning

confidence: 91%

“…Therefore, insulin release and clearance are altered to promote hyperinsulinaemia in the lard‐fed animals (Figure ). In comparison, as there is no insulin resistance to compensate for, the PUFA diet does not alter insulin clearance, and may even reduce insulin release . These results on hyperinsulinaemia occur in response to insulin resistance, but without effect on plasma glucose levels, which suggests that hyperinsulinaemia develops in response to insulin resistance.…”

Section: Skeletal Musclementioning

confidence: 93%

“…The lard diet induced hyperinsulinaemia and a reduction in insulin sensitivity. Yet the PUFA fed animals maintained normal insulin sensitivity, and even had a lower plasma insulin level, in spite of a similar level of obesity . This study also investigated cardiac parameters, and while the short diet intervention did not impact cardiac output or other clinical measures of heart function, subclinical measures of heart function that were impaired by a lard‐based diet were not impacted by PUFA diets .…”

Section: Skeletal Musclementioning

confidence: 94%

“…Yet the PUFA fed animals maintained normal insulin sensitivity, and even had a lower plasma insulin level, in spite of a similar level of obesity. 67 This study also investigated cardiac parameters, and while the short diet intervention did not impact cardiac output or other clinical measures of heart function, subclinical measures of heart function that were impaired by a lard-based diet were not impacted by PUFA diets. 68 These heart function effects may be due to a change in the fuel preference and availability for the heart but may also have been impacted by changes in the cardiac microvasculature; this requires further study.…”

Section: S K Ele Tal Musclementioning

confidence: 99%

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The vascular endothelium plays a role in insulin action

Kolka

2019

Clin Exp Pharma Physio

Self Cite

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The endocrine system relies on the vasculature for delivery of hormones throughout the body, and the capillary microvasculature is the site where the hormones cross from the blood into the target tissue. Once considered an inert wall, various studies have now highlighted the functions of the capillary endothelium to regulate transport and therefore affect or maintain the interstitial environment. The role of the capillary may be clear in areas where there is a continuous endothelium, yet there also appears to be a role of endothelial cells in tissues with a sinusoidal structure. Here we focused on the most common endocrine disorder, diabetes, and several of the target organs associated with the disease, including skeletal muscle, liver and pancreas. However, it is important to note that the ability of hormones to cross the endothelium to reach their target tissue is a component of all endocrine functions. It is also a consideration in organs throughout the body and may have greater impact for larger hormones with target tissues containing a continuous endothelium. We noted that the blood levels do not always equal interstitial levels, which is what the cells are exposed to, and discussed how this may change in diseases such as obesity and insulin resistance. The capillary endothelium is, therefore, an essential and understudied aspect of endocrinology and metabolism that can be altered in disease, which may be an appropriate target for treatment.

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Integration analysis of transcriptome and proteome of Chinese Merino sheep (Ovis aries) embryonic skeletal muscle

Feng,

Hu,

Wang

et al. 2023

Animal Research and One Health

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The growth and development of sheep late fetal skeletal muscle undergoes significant changes. However, the specific mechanism remains unknown. In this study, we performed the comprehensive analysis of transcriptome and proteome of Chinese Merino sheep at embryonic ages Day85 (D85N), Day105 (D105N), and Day135 (D135N) by the tandem mass tags (TMT) and RNA‐seq methods. Totally 717, 1253, and 1873 differentially expressed genes (DEGs) were identified in the three comparison groups (D85N vs. D105N, D105N vs. D135N, and D85N vs. D135N). Among which 7, 80, and 162 DEGs were identified with the same trends at mRNA and protein levels in the three groups. Enrichment analysis showed that 7 genes with same trends in D85 vs. D105 have not been enriched in any pathways, which indicated that the development of skeletal muscle underwent significant changes with post‐transcription regulation during this period. These genes with same trends in D105N vs. D135N were mainly enriched in the pathways related to skeletal muscle metabolism and maturation, including oxidative phosphorylation, glycolysis/gluconeogenesis, tight junction, and HIF‐1 pathways, which indicated that the development of skeletal muscle tended to maturation during this period. These results provided evidence for ovine late fetal skeletal muscle fibers development from proliferating to thickening at simultaneous transcriptional and translational levels.

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Insulin Access to Skeletal Muscle is Preserved in Obesity Induced by Polyunsaturated Diet

Cited by 7 publications

References 31 publications

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

Insulin uptake and action in microvascular endothelial cells of lymphatic and blood origin

The vascular endothelium plays a role in insulin action

Integration analysis of transcriptome and proteome of Chinese Merino sheep (Ovis aries) embryonic skeletal muscle

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