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Fatty acids and glucolipotoxicity in the pathogenesis of Type 2 diabetes
- Source :
- Biochemical Society transactions, 36 (Pt 3
- Publication Year :
- 2008
-
Abstract
- The prevalence of Type 2 diabetes is increasing dramatically as a result of the obesity epidemic, and poses a major health and socio-economic burden. Type 2 diabetes develops in individuals who fail to compensate for insulin resistance by increasing pancreatic insulin secretion. This insulin deficiency results from pancreatic beta-cell dysfunction and death. Western diets rich in saturated fats cause obesity and insulin resistance, and increase levels of circulating NEFAs [non-esterified ('free') fatty acids]. In addition, they contribute to beta-cell failure in genetically predisposed individuals. NEFAs cause beta-cell apoptosis and may thus contribute to progressive beta-cell loss in Type 2 diabetes. The molecular pathways and regulators involved in NEFA-mediated beta-cell dysfunction and apoptosis are beginning to be understood. We have identified ER (endoplasmic reticulum) stress as one of the molecular mechanisms implicated in NEFA-induced beta-cell apoptosis. ER stress was also proposed as a mechanism linking high-fat-diet-induced obesity with insulin resistance. This cellular stress response may thus be a common molecular pathway for the two main causes of Type 2 diabetes, namely insulin resistance and beta-cell loss. A better understanding of the molecular mechanisms contributing to pancreatic beta-cell loss will pave the way for the development of novel and targeted approaches to prevent Type 2 diabetes.<br />Journal Article<br />Research Support, Non-U.S. Gov't<br />Review<br />info:eu-repo/semantics/published
- Subjects :
- medicine.medical_specialty
Lipotoxicily
Apoptosis
Type 2 diabetes
Biology
Biochemistry
Pathogenesis
Insulin resistance
Diabetes mellitus
Internal medicine
Cellular stress response
medicine
Animals
Humans
Secretion
Non-esterified fatty acid
Lipoprotein
Pancreatic β-cell
Fatty Acids -- toxicity
Fatty Acids
Sciences bio-médicales et agricoles
Diabetes Mellitus, Type 2 -- pathology
medicine.disease
Obesity
Glucose
Endocrinology
Diabetes Mellitus, Type 2
Unfolded protein response
Glucose -- toxicity
Médecine clinique [biologie clinique]
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Biochemical Society transactions, 36 (Pt 3
- Accession number :
- edsair.doi.dedup.....93496a547e27857888074a13caf1a7c1