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|Title:||Obesity and type 2 diabetes: slow down!--Can metabolic deceleration protect the islet beta cell from excess nutrient-induced damage?|
|Affiliation:||Department of Medicine (AH/NH), University of Melbourne, Heidelberg Repatriation Hospital, Heidelberg Heights, Victoria, Australia|
|Citation:||Molecular and Cellular Endocrinology 2009; 316(2): 140-6|
|Abstract:||Islet beta-cell dysfunction is a characteristic and the main cause of hyperglycaemia of Type 2 diabetes. Understanding the mechanisms that cause beta-cell dysfunction will lead to better therapeutic outcomes for patients with Type 2 diabetes. Chronic fatty acid exposure of susceptible islet beta-cells causes dysfunction and death and this is associated with increased reactive oxygen species production leading to oxidative stress and increased endoplasmic reticulum stress. We present the hypothesis that metabolic deceleration can reduce both oxidative and endoplasmic reticulum stress and lead to improved beta-cell function and viability when exposed to a deleterious fat milieu. This is illustrated by the C57BL/6J mouse which is characterised by reduced insulin secretion and glucose intolerance associated with a mutation in nicotinamide nucleotide transhydrogenase (Nnt) but is resistant to obesity induced diabetes. On the other hand the DBA/2 mouse has comparatively higher insulin secretion and better glucose tolerance associated with increased Nnt activity but is susceptible to obesity-induced diabetes, possibly as a result of increased oxidative stress. We therefore suggest that in states of excess nutrient load, a reduced ability to metabolise this load may protect both the function and viability of beta-cells. Strategies that reduce metabolic flux when beta-cells are exposed to nutrient excess need to be considered when treating Type 2 diabetes.|
|Internal ID Number:||19815054|
Diabetes Mellitus, Type 2.metabolism.pathology.physiopathology
Fatty Acids, Nonesterified.metabolism
Mice, Inbred C57BL
Mice, Inbred DBA
|Appears in Collections:||Journal articles|
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