ReviewEndogenous peptides as risk markers to assess the development of insulin resistance
Introduction
Insulin resistance is an important functional and clinical state characterized by a decrease in efficiency of insulin signaling for blood sugar regulation. As a consequence, myocytes, hepatocytes and adipocytes take up less glucose and the blood glucose concentration is elevated [93]. In nondiabetic individuals, a herald of the possibility of insulin resistance includes obesity, hyperinsulinemia, dyslipidemia, hypertension and impaired glucose tolerance [32], [67], [75]. The close relationship between insulin resistance and subclinical or clinical diseases has been observed, including cardio-vascular diseases [34], [97], neurodegenerative disorders [43], [89], infectious diseases [41], cancer [11] and metabolic syndrome in both nondiabetic [10], [37], [47] and diabetic subjects [9], [39]. Despite extensive investigations into insulin resistance, the precise mechanism is inadequately comprehended as yet. There are numerous factors involved in pathogenesis and mechanisms of insulin resistance, including the obesity, smoking, pregnancy, genes alteration, endocrine disorders, chromium lack and so on. Due to the ongoing worldwide epidemic of insulin resistance-related disorders [13], there is a pressing need to evaluate the insulin resistance status precisely and promptly. Quantifying insulin resistance in animal model and human is vitally important for basic scientific investigation and clinical practice [64].
Currently, a measure of plasma biomarker is an efficient predictor of insulin resistance and subsequent disorders, but validated risk-assessment methods about insulin resistance are not satisfactory enough in the clinical practice. To date a number of peptides and proteins, including galanin, galanin-like peptide (GALP), ghrelin, adiponectin, retinol binding protein 4 (RBP4) and C-reactive protein (CRP), have been identified as important biomarkers of developing insulin resistance, as they all respond to glucose intake in a dose-dependent manner. This review reports the updated information about these peptides, highlighting the effects of these endocrine peptide levels on insulin resistance and glucose homeostasis. It may foresee that this research line will help us better understanding and exploitation of the underlying mechanism of evolutionary insulin resistance to predict relative diseases.
Section snippets
Galanin
Galanin, a 29/30 amino-acid peptide, was isolated in 1983 from porcine intestine by Tatemoto and collaborators [92]. This peptide distributes widely throughout the peripheral and central nervous system as well as other tissues, such as the liver, skeletal muscle and adipose tissue, which are the main tissues to regulate insulin sensitivity and glucose disposal [24]. Galanin modulates a variety of biological functions, liking depression [80], feeding [25], pain threshold control [106], neuronal
Ghrelin
Ghrelin is a 28 amino acid gut-brain peptide, which is originally isolated from rat stomach by Kojima et al. in 1999 [44]. Uniquely, ghrelin is post-translationally modified with an octanoyl side chain on serine position 3, which is required for its activity as removed the acyl group the peptide is completely inactive. This gut-brain peptide is mainly produced in the stomach and distributed widely throughout lungs, gonads, pancreatic islets, adrenal cortex, kidney, placenta and brain [18].
Conclusion
Assessment of insulin resistance is increasingly being exploited in clinic and research activities, and this calls for the further search of relatively simple and stable markers. Although numerous factors are involved in insulin resistance, the endocrine proteins and peptides play a crucial role in the developing insulin resistance. Current researches have recommended these endocrine protein and peptide contents as surrogate markers, liking plasma high ghrelin, RBP4 and CRP as well as low
Conflict of interest
The authors have no conflicts of interest to disclose.
Acknowledgements
This work was supported by the Grant of National Natural Scientific Fund of China to Ping Bo (81173392) and in part by the Grant of National Health and Family Planning Commission of China (W201309) to Zhenwen Zhang.
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2017, Mechanisms of Ageing and DevelopmentCitation Excerpt :The molecular mechanisms for increased insulin resistance in skeletal muscle should be further explored. The recent studies showed that the administration of galanin can regulate energy metabolism and glucose homeostasis of animals and humans with diabetes and obesity (Fang et al., 2014a, 2012a, 2012b). The intracerebroventricular (i.c.v.) injection of galanin directly into paraventricular nucleus (PVN) significantly enhanced daily caloric intake, weight of fat depots, circulating non-esterified fatty acids content and lipoprotein lipase activity in adipose tissue, but reduced circulating glucose levels of rats (Yun et al., 2005).