Browsing by Author "Ostenson,Claes-Goran"

Now showing 1 - 2 of 2

Genetic Association of Adrenergic Receptor Alpha 2a with Obesity and Type 2 Diabetes
(Original Article EPIDEMIOLOGY/GENETICS, 2013) La ̊ ngberg,Ewa-Carin; Ahmed,Mohammed Seed; Efendic,Suad; Gu,Harvest F; Ostenson,Claes-Goran
Objective: The sympathetic nervous system (SNS) is linked to glucose, lipid, and protein metabolism. The a2A-adrenergic receptor (ADRA2A) is involved in the SNS and mediates inhibition of insulin secretion and lipolysis. The association of ADRA2A single-nucleotide polymorphisms (SNPs) with obesity and/or type 2 diabetes (T2D) was investigated. Design and Methods: Genotyping was performed in a case–control study of 1,177 Swedish individuals, including lean and obese subjects with normal glucose tolerance (NGT) and T2D patients. ADRA2A mRNA expression was measured in pancreatic islets isolated from T2D patients and nondiabetic subjects. Results: SNP rs553668 was associated with T2D in men (odds ratio [OR] 1⁄4 1.47; 95% confidence interval [CI] 1⁄4 1.08–2.01; P 1⁄4 0.015) but this association was lost after adjusting for age and for body mass index (BMI). Associations were also detected when comparing obese NGT and lean NGT subjects (OR 1⁄4 1.49; 95% CI 1⁄4 1.07–2.07; P 1⁄4 0.017), and in obese (OR 1⁄4 1.62; 95% CI 1⁄4 1.06–2.49; P 1⁄4 0.026), but not in lean T2D. In women, multiple logistic regression regarding SNP rs521674 demonstrated an increased OR of 7.61 (95% CI 1⁄4 1.70–34.17; P 1⁄4 0.008) for T2D when including age as a covariant. Correcting for BMI removed the significant association. When age was included in the model, association also found when obese T2D patients were compared with lean NGT subjects (P 1⁄4 0.041). ADRA2A mRNA expression in human pancreatic islets was detectable, but with no statistically significant difference between the diabetic and the control groups. Conclusions: ADRA2A genetic polymorphisms are mainly associated with obesity and possibly with T2D in a Swedish population.
Lower succinyl-CoA:3-ketoacid-CoA transferase (SCOT) and ATP citrate lyase in pancreatic islets of a rat model of type 2 diabetes: Knockdown of SCOT inhibits insulin release in rat insulinoma cells
(journal homepage: www.elsevier.com/locate/yabbi, 2010) Hasan,Noaman M; Longacre,Melissa J; Ahmed,Mohammed Seed; Kendrick,Mindy A; Gu,Harvest; Ostenson,Claes-Goran; Fukao,Toshiyuki; MacDonald,Michael J
Succinyl-CoA:3-ketoacid-CoA transferase (SCOT) is a mitochondrial enzyme that catalyzes the reversible transfer of coenzyme-A from acetoacetyl-CoA to succinate to form acetoacetate and succinyl-CoA. mRNAs of SCOT and ATP citrate lyase were decreased 55% and 58% and enzyme activities were decreased >70% in pancreatic islets of the GK rat, a model of type 2 diabetes. INS-1 832/13 cells were transfected with shR- NAs targeting SCOT mRNA to generate cell lines with reduced SCOT activity. Two cell lines with >70% knockdown of SCOT activity showed >70% reduction in glucose- or methyl succinate-plus-b-hydroxybu- tyrate-stimulated insulin release. Less inhibition of insulin release was observed with two cell lines with less knockdown of SCOT. Previous studies showed knockdown of ATP citrate lyase in INS-1 832/13 cells does not lower insulin release. The results further support work that suggests mitochondrial pathways involving SCOT which supply acetoacetate for export to the cytosol are important for insulin secretion.