title: Initial hyperinsulinemia and subsequent β-cell dysfunction is associated with elevated palmitate levels.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Staaf
authors.affiliation: Department of Chemistry-BMC, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Sarojini J K A
authors.initials: SJ
authors.lastname: Ubhayasekera
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Ernest
authors.initials: E
authors.lastname: Sargsyan
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Azazul
authors.initials: A
authors.lastname: Chowdhury
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Hjalti
authors.initials: H
authors.lastname: Kristinsson
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.|Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Hannes
authors.initials: H
authors.lastname: Manell
authors.affiliation: Department of Chemistry-BMC, Analytical Chemistry and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergquist
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Forslund
authors.affiliation: Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Bergsten
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000737:chemistry; D005260:Female; D005947:Glucose / Q000494:pharmacology; D005951:Glucose Tolerance Test; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications; D010168:Palmitates / Q000097:blood*; D063766:Pediatric Obesity; D013997:Time Factors
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D010168:Palmitates; D005947:Glucose