PINK1 deficiency in β-cells increases basal insulin secretion and improves glucose tolerance in mice
| Autor: | Dominic J. Withers, Emma Deas, Ana Gutierrez-del-Arroyo, Abi Li, Kaisa Piipari, Asif Machhada, Andrey Y. Abramov, Nicholas W. Wood |
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| Rok vydání: | 2014 |
| Předmět: |
insulin
medicine.medical_specialty Glucose uptake medicine.medical_treatment Immunology β-cells Type 2 diabetes Carbohydrate metabolism Biology General Biochemistry Genetics and Molecular Biology Diabetes Mellitus Experimental Islets of Langerhans Mice Insulin-Secreting Cells Internal medicine Insulin Secretion medicine Animals RNA Small Interfering pink1 lcsh:QH301-705.5 Cells Cultured Mice Knockout Glucose tolerance test diabetes medicine.diagnostic_test Research General Neuroscience Insulin Glucose Tolerance Test medicine.disease Mitochondria Insulin oscillation Glucose Endocrinology lcsh:Biology (General) Basal (medicine) parkinson's disease Calcium RNA Interference Reactive Oxygen Species Protein Kinases Homeostasis Research Article |
| Zdroj: | Open Biology, Vol 4, Iss 5 (2014) Open Biology |
| ISSN: | 2046-2441 |
| DOI: | 10.1098/rsob.140051 |
| Popis: | The Parkinson's disease (PD) gene, PARK6 , encodes the PTEN-induced putative kinase 1 (PINK1) mitochondrial kinase, which provides protection against oxidative stress-induced apoptosis. Given the link between glucose metabolism, mitochondrial function and insulin secretion in β-cells, and the reported association of PD with type 2 diabetes, we investigated the response of PINK1-deficient β-cells to glucose stimuli to determine whether loss of PINK1 affected their function. We find that loss of PINK1 significantly impairs the ability of mouse pancreatic β-cells (MIN6 cells) and primary intact islets to take up glucose. This was accompanied by higher basal levels of intracellular calcium leading to increased basal levels of insulin secretion under low glucose conditions. Finally, we investigated the effect of PINK1 deficiency in vivo and find that PINK1 knockout mice have improved glucose tolerance. For the first time, these combined results demonstrate that loss of PINK1 function appears to disrupt glucose-sensing leading to enhanced insulin release, which is uncoupled from glucose uptake, and suggest a key role for PINK1 in β-cell function. |
| Databáze: | OpenAIRE |
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