Elsevier

Peptides

Volume 51, January 2014, Pages 9-14
Peptides

Review
Endogenous peptides as risk markers to assess the development of insulin resistance

https://doi.org/10.1016/j.peptides.2013.10.025Get rights and content

Highlights

  • Marker peptides for assessing the risk of insulin resistance.

  • High ghrelin, RBP4 and CRP levels as the markers of deteriorating IR.

  • Low galanin, GALP and adiponectin levels as the markers of deteriorating IR.

Abstract

Insulin resistance, the reciprocal of insulin sensitivity, is known to be a characteristic of type 2 diabetes mellitus, and is regarded as an important mechanism in the pathogenesis. The hallmark of insulin resistance is a gradual break-down of insulin-regulative glucose uptake by muscle and adipose tissues in subjects. Insulin resistance is increasingly estimated in various disease conditions to examine and assess their etiology, pathogenesis and consequences. Although our understanding of insulin resistance has tremendously been improved in recent years, certain aspects of its estimation and etiology still remain elusive to clinicians and researchers. There are numerous factors involved in pathogenesis and mechanisms of insulin resistance. Recent studies have provided compelling clues about some peptides and proteins, including galanin, galanin-like peptide, ghrelin, adiponectin, retinol binding protein 4 (RBP4) and CRP, which may be used to simplify and to improve the determination of insulin resistance. And alterations of these peptide levels may be recognized as risk markers of developing insulin resistance and type 2 diabetes mellitus. This review examines the updated information for these peptides, highlighting the relations between these peptide levels and insulin resistance. The plasma high ghrelin, RBP4 and CRP as well as low galanin, GALP and adiponectin levels may be taken as the markers of deteriorating insulin resistance. An increase in the knowledge of these marker proteins and peptides will help us correctly diagnose and alleviate insulin resistance in clinic and study.

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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