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Published on: June 25, 2017
Initial hyperinsulinemia and subsequent β-cell dysfunction is associated with elevated palmitate levels
Johan Staaf1,2, Sarojini J K A Ubhayasekera3, Ernest Sargsyan1
1Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Insights
Elevated palmitate levels in obese children and adolescents are linked to altered insulin secretion. This suggests that fatty acid exposure impacts pancreatic islet function, potentially contributing to diabetes development.
Area of Science:
- Endocrinology
- Metabolic disorders
- Pediatric research
Background:
- Childhood obesity and diabetes prevalence are rising.
- Nonesterified fatty acids, like palmitate, may link obesity to diabetes.
- Understanding palmitate's role in insulin secretion is crucial.
Purpose of the Study:
- To investigate the association between palmitate and insulin secretion in children and adolescents.
- To examine the in vivo and in vitro effects of palmitate on pancreatic islet function.
Main Methods:
- Studied 80 obese and lean children/adolescents, measuring fasting palmitate and glucose-stimulated insulin secretion (OGTT).
- Cultured human islets with palmitate, assessing glucose-stimulated insulin secretion (GSIS), insulin content, and apoptosis.
- Analyzed palmitate levels, insulin response during OGTT, GSIS, insulin content, and apoptosis markers.
Main Results:
- Obese subjects showed higher fasting palmitate levels.
- Elevated palmitate correlated with accentuated insulin levels in younger obese children but delayed first-phase insulin response in obese adolescents.
- In vitro, palmitate initially enhanced GSIS but attenuated it after 7 days, while decreasing insulin content and increasing apoptosis.
Conclusions:
- High palmitate levels in obese youth are associated with altered insulin secretory patterns.
- These changes in insulin secretion and islet integrity may be induced by prolonged palmitate exposure.
- Palmitate's impact on pancreatic islets could be a key factor in obesity-related diabetes development.
Background:
The prevalence of obesity-related diabetes in childhood is increasing and circulating levels of nonesterified fatty acids may constitute a link. Here, the association between palmitate and insulin secretion was investigated in vivo and in vitro.
Methods:
Obese and lean children and adolescents (n = 80) were included. Palmitate was measured at fasting; insulin and glucose during an oral glucose tolerance test (OGTT). Human islets were cultured for 0 to 7 d in presence of 0.5 mmol/l palmitate. Glucose-stimulated insulin secretion (GSIS), insulin content and apoptosis were measured.
Results:
Obese subjects had fasting palmitate levels between 0.10 and 0.33 mmol/l, with higher average levels compared to lean subjects. While obese children with elevated palmitate (>0.20 mmol/l) had accentuated insulin levels during OGTT, obese adolescents with high palmitate had delayed first-phase insulin response. In human islets exposed to palmitate for 2 d GSIS was twofold enhanced, but after 7 d attenuated. Intracellular insulin content decreased time-dependently in islets cultured in the presence of palmitate and cleaved caspase 3 increased.
Conclusion:
The rapid accentuated and delayed insulin secretory responses observed in obese children and adolescents, respectively, with high palmitate levels may reflect changes in islet secretory activity and integrity induced by extended exposure to the fatty acid.
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