Xenobiotic mediated diabetogenesis: Developmental exposure to dichlorvos or atrazine leads to type 1 or type 2 diabetes in Drosophila
| Autor: | Devendra Kumar Patel, Himanshu Pawankumar Gupta, Rakesh Roshan Jha, Kristipati Ravi Ram, Humaira Ahmad |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty medicine.medical_treatment Gene Expression Apoptosis Type 2 diabetes Biochemistry Xenobiotics 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Physiology (medical) Diabetes mellitus Internal medicine medicine Animals Homeostasis Humans Insulin Glucose homeostasis Type 1 diabetes biology Superoxide Dismutase JNK Mitogen-Activated Protein Kinases medicine.disease Disease Models Animal Oxidative Stress Insulin receptor Diabetes Mellitus Type 1 Drosophila melanogaster 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 chemistry Dichlorvos biology.protein Atrazine Insulin Resistance Xenobiotic Oxidation-Reduction 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | Free Radical Biology and Medicine. 141:461-474 |
| ISSN: | 0891-5849 |
| Popis: | The increased incidence of diabetes to the magnitude of a global epidemic is attributed to non-traditional risk factors, including exposure to environmental chemicals. However, the contribution of xenobiotic exposure during the development of an organism to the etiology of diabetes is not fully addressed. Developing stages are more susceptible to chemical insult, but knowledge on the consequence of the same to the onset of diabetes is residual. In this context, by using Drosophila melanogaster having conserved Insulin/Insulin growth factor-like signaling (IIS) as well as glucose homeostasis as a model, we evaluated the potential of developmental exposure to dichlorvos (DDVP, an organophosphorus pesticide) or atrazine (herbicide) to cause diabetes in exposed organisms. Flies exposed to DDVP during their development display insulin deficiency or type 1 diabetes (T1D) while those exposed to atrazine show insulin resistance or type 2 diabetes (T2D), suggesting that exposure to these xenobiotics during organismal development can result in diabetes and that different mechanisms underlie pesticide mediated diabetes. We show that oxidative stress-mediated c-Jun N-terminal kinase (JNK) signaling activation underlies insulin resistance in flies exposed to atrazine during their development while DDVP-mediated T1D involves activation of caspase-mediated cell death pathway. Mitigation of oxidative stress through over-expression of SOD2 in atrazine (20μg/ml) exposed flies, revealed significantly decreased oxidative stress levels and reduced phosphorylation of JNK. Moreover, glucose and Akt phosphorylation levels in SOD2 over-expression flies exposed to atrazine were comparable to those in controls, suggesting restoration in insulin sensitivity. Therefore, exposure to xenobiotics during development is a common risk factor for the development of type 1 or type 2 diabetes. Accordingly, the present study cautions against the use of such diabetogenic pesticides. Also, mitigation of oxidative stress or anti-oxidant supplementation could be a potential therapy for xenobiotic mediated type 2 diabetes. |
| Databáze: | OpenAIRE |
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