Possible Mechanisms of Insulin Resistance in Obese Subjects

Hala Mourad Demerdash

Assistant Professor Department of Clinical Pathology Pharos University Hala Mourad Demerdash, MD Alexandria, EgyptEgypt

DOI: https://doi.org/10.17140/oroj-2-118 · Published 2015-03-15 · Licence: https://creativecommons.org/licenses/by/4.0 · © 2015 The Author(s)

Also available as PDF (figures and tables appear in the PDF).

Keywords: triglyceride; adipocytes

ISSN 2377-8385 http://dx.doi.org/10.17140/OROJ-2-118 Open Journal Letter to the Editor Possible Mechanisms of Insulin Resistance * *Corresponding author in Obese Subjects Hala Mourad Demerdash, MD Assistant Professor Department of Clinical Pathology * Pharos University Hala Mourad Demerdash, MD* Alexandria, Egypt E-mail: demerdashh@yahoo.com Department of Clinical Pathology, Pharos University, Alexandria, Egypt Volume 2 : Issue 4 Article Ref. #: 1000OROJ2118 Obesity is characterized by excessive triglyceride accumulation in adipose tissue cells (adipocytes); the adipocytes are not just a reservoir for storage of energy in the form of triglyc- Article History eride, but more importantly act as endocrine cells; they secrete several hormones as leptin and th Received: March 10th, 2016 adiponectin, also secrete adipokines as TNF-α, Interleukin 6 (IL-6) and Plasminogen activator th Accepted: March 14th, 2016 inhibitor-1 (PAI-1). In obese subjects, adipocytes release high levels of free fatty acids (FFA) th Published: March 15th, 2016 and its metabolites; Diacylglycerol (DAG) and ceramide.

Citation Acquired insulin resistance is associated with obesity. Insulin resistance is classically Demerdash HM. Possible mech- defined as impaired insulin-mediated glucose disposal in skeletal muscle. There are several anisms of insulin resistance mechanisms responsible for insulin resistance in obese subjects, which can be classified into in obese subjects. Obes Res Open J. 2016; 2(4): 117-118. either to activation of inflammatory pathways or changes in lipoproteins and apoprotein con- 1,2 doi: 10.17140/OROJ-2-118 centrations as result of associated dyslipidemias.1,2 Those mechanisms include; inflammatory pathways through activation of (IKKβ) (inhibitor of nuclear factor κB) and c-Jun N-terminal kinase 1 (JNK1): They play a role in feedback inhibition of the insulin signaling cascade. Their activation occur by increased secre- tion of free fatty acids (FFA) and its metabolites, which together adipokines (TNF-α), reac- tive oxygen species in both liver and adipose tissue. The resultant activation of JNK1 stimu- lates serine phosphorylation of insulin receptor substrate 1 (IRS-1) with a resultant decline in insulin signaling.3 The second is inhibition of Peroxisome proliferator-activated receptor gamma (PPARγ) by TNF-α; PPARγ is a nuclear receptor that stimulates enzymes and/ proteins involved in fatty acid esterification and triglyceride synthesis and degradation. Its inhibition decreases triglyceride storage in adipocytes and increases lipid distribution to skeletal muscle and liver which consequently contributes to insulin resistance.4 Also Leptin and adiponectin under normal conditions promote FA oxidation, lower lipid stores. Those effects are mediated through AMP-activated protein kinase. However; some degree of resistance to each of these adipokines in skeletal muscle develops in obese subjects leading to accumulation of DAG and ceramide, with resultant increase in FFA uptake and decreased oxidation, leading to impaired insulin signaling.5 Moreover, hepatocytes and adipocytes are the major sources of apolipoproteins. Apo- proteins are the proteins of lipoproteins. They have several functions, for example some are known to regulate lipolytic enzyme activities and lipoprotein uptake into cells. Also some ra- tios of those apoproteins may be used as indicators of dyslipidemias. In addition, they exert an influence on insulin sensitivity either directly or through lipoproteins.2 There are several types of apoproteins: Copyright ©2016 Demerdash HM. This is an Apolipoprotein (Apo A) is a major component of high density lipoproteins (HDL-C); open access article distributed un- apolipoprotein A-I (ApoA1) indirectly modulates insulin sensitivity through their antioxidant der the Creative Commons Attribu- and anti-inflammatory action. apoA-I and apoA-II are reported to have incretin-like properties; tion 4.0 International License (CC incretins such as glucagon-like peptide-1 (GLP-1) and the glucose-dependent insulinotropic BY 4.0), which permits unrestricted use, distribution, and reproduction (GIP), are small peptides secreted from the gut in response to glucose, they stimulate insu- in any medium, provided the origi- lin secretion from β-cells of pancreas. In addition, apoA-I and apoA-II both increase insulin nal work is properly cited.

secretion under basal as well as high glucose concentrations. In contrast to incretins which ISSN 2377-8385 http://dx.doi.org/10.17140/OROJ-2-118 Open Journal stimulate insulin secretion from β-cells only under high glucose obesity-associated diabetes and its complications.

concentrations. Also apoA-IV is similar to endogenous incretins, it stimulates insulin secretion from β-cells only under high glu-

References

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