Elsevier

Biomedicine & Pharmacotherapy

Volume 102, June 2018, Pages 354-361
Biomedicine & Pharmacotherapy

Experimental diabetes induced by streptozotocin in the desert gerbil, Gerbillus gerbillus, and the effects of short-term 20-hydroxyecdysone administration

https://doi.org/10.1016/j.biopha.2018.03.070Get rights and content

Highlights

  • We examined the effects of streptozotocin and 20-hydroxyecdysone in gerbils.

  • 20E has a beneficial effect on glucose homeostasis in STZ-treated gerbils.

  • 20E reduced lipid peroxidation in the pancreas of STZ-treated gerbils.

  • 20E may stimulate pancreatic β-cells to release more insulin.

  • Gerbils are an interesting model to study diabetes and test new therapeutic agents.

Abstract

The present work was aimed at studying the effects of streptozotocin (STZ; 130 mg/kg) in the desert gerbil, Gerbillus gerbillus, and at evaluating the impact of the short-term administration of 20-hydroxyecdysone (20E; 5 mg/kg). We observed that administration of streptozotocin caused a significant increase in plasmatic glucose and a decrease in insulin levels. The plasma lipid profile and liver glycogen content were also altered. The activities of antioxidant enzymes and malondialdehyde (MDA) levels were increased in the pancreatic tissue of STZ-treated gerbils. Moreover, histopathological and immunohistochemical analysis showed degenerative damage in the pancreas with a decline in the percentage area of β-cells. Treatment of STZ-treated gerbils with 20E counteracted metabolic disorders and reduced lipid peroxidation. Histological and immunohistochemical studies showed moderate amelioration in the pancreatic structure. These findings indicate that streptozotocin administration induced experimental diabetes in gerbils and that short-term administration of 20E has beneficial effects in glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate surviving β-cells to release more insulin.

Introduction

Diabetes mellitus is a metabolic disease characterized by impairment in carbohydrate, fat and protein metabolism with defects in insulin secretion, insulin action or both. Diabetes affects approximately 8.3% of the people in the world. According to the data of the International Federation of Diabetes, the prevalence of diabetes is predicted to rise to 10.4% in 2040 [1].Chronic hyperglycaemia and subsequent increase in oxidative stress are thought to contribute to progressive dysfunction of pancreatic β-cells and to the development of diabetic complications by altering the capacities of various tissues and organs such as eyes, liver, muscle, kidney and pancreas. Several lines of evidence indicate that persistent hyperglycaemia could exacerbate dysfunction of the islets of Langerhans by inducing β-cell apoptosis [2]. The complications of diabetes are a major cause of mortality and morbidity and are associated with very high economic and social costs. Total global health expenditure on diabetes was estimated at 673 billion US dollars for 2015 and 802 billion US dollars for 2040 [1].

Several animal models have been developed for studying diabetes. These models have elucidated complex mechanisms that underlie the development of diabetes and its complications, but none of the existing animal models can completely mimic all the features of human diabetes [3]. Moreover, animal models of diabetes have limitations such as extensive use of animals, high mortality rates, and being expensive and time-consuming [4,5].

The development of new improved models of diabetes is needed to mimic different aspects of this pathology, to identify new therapeutic targets and agents and to reassess existing treatments. Gerbils are particularly interesting for the study of diabetes and obesity as these outbred models develop metabolic, physiological and endocrine changes similar to those occurring in humans as revealed by studies on Psammomys obesus [6] and Mongolian gerbils [7].

Streptozotocin is a glucosamine nitrosourea derivative isolated from Streptomyces achromogenes used in single large doses to induce hyperglycaemia or in multiple low doses to induce experimental Type-1 diabetes in animal models through its toxic effects in pancreatic β-cells. STZ enters β-cells via the GLUT2 glucose transporter [8]. The cytotoxic action of STZ occurs through the synergistic actions of DNA alkylation followed by fragmentation of DNA and the activation of poly-ADP-ribose polymerase, resulting in inhibition of the synthesis and secretion of insulin [8,9]. Studies have shown that streptozotocin induces oxidative stress in β-cells and caused DNA alkylation with necrosis. Overexpression of antioxidant enzymes protects the islets from streptozotocin toxicity [10].

Ecdysteroids were originally isolated from insects, where they play important roles in moulting and reproduction. Ecdysteroids are also present in 5–6% of plant species where they are implicated in the deterrence of invertebrate predators [11,12]. The major phytoecdysteroid found in plants is 20-hydoxyecdysone (20E) [13]. Numerous studies report that 20E may have beneficial activities in mammals by affecting aspects of protein, lipid and carbohydrate metabolism [14]. It has been shown that 20E administration improved glucose homeostasis, lipid metabolism and pancreatic damage in STZ-induced diabetic rats [15]. The aim of the present work was to study effects of streptozotocin on carbohydrate metabolism, lipid profile and on the pancreas in gerbils and to evaluate the short-term impact of 20E administration.

Section snippets

Chemicals

Streptozotocin (STZ) was purchased from Sigma–Aldrich (Germany). 20-Hydroxyecdysone (20E; 95% purity) was extracted from Cyanotis vaga and purchased from Changzou Dahua Import and Export Inc., Changzou, China. All other chemicals used were of analytical grade.

Animals

Male adult gerbils (Gerbillus gerbillus), weighing 20–30 g were used in the present work. Gerbils were captured in the semi-desert Algerian region of Beni-Abbes, in association with the Algiers-Beni-Abbes Research Station (Wilaya of Bechar

Effects of STZ and 20E on plasma glucose, insulin and lipid metabolism

Table 1 shows the effects of STZ and 20E on plasma glucose level of control and experimental groups of gerbils. A single dose of streptozotocin induced a significant increase of plasma glucose when compared to the control group. Administration of 20E to STZ-treated gerbils induced a significant decrease of plasma glucose when compared to the STZ-treated animals. Three hours after administration of 20E, plasmatic glucose of STZ-treated gerbils was reduced significantly when compared to the

Discussion

Gerbils are considered as potential models for the study of diabetes and its complications. They develop spontaneously (Mongolian gerbil), or after a change in diet (Psammomys obesus), symptoms similar to those observed in humans [6,7]. Gerbils exhibit variations in responses between individuals which closely resemble the human diabetic phenotype. In this respect, using natural populations of a wild animal provide an experimental material which, thanks to its heterogeneity appears more

Conclusion

The present study indicates that administration of streptozotocin to gerbils induced metabolic disorders, oxidative stress and β-cell damage. Treatment with 20E has beneficial effects in glucose homeostasis in STZ-treated gerbils suggesting that 20E may stimulate surviving β-cells to release more insulin. Future experiments will be aimed at investigating the effects of long-term administration of 20E on STZ-treated gerbils.

Funding source

This work was supported by the Algerian Ministry of Higher Education and Scientific Research.

Conflict of interest

There is no conflict of interest.

Acknowledgements

We thank Dr. Laurence Dinan for reading and commenting on the manuscript. We also thank Pr. Ahmed Menad for technical assistance.

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