Nor-1, a novel incretin-responsive regulator of insulin genes and insulin secretion.

B-cell failure at the onset of type 2 diabetes is caused by a decline in β-cell function in the postprandial state and loss of pancreatic β-cell mass. Recently, we showed an association between increased insulin secretion and a single nucleotide polymorphism (SNP), SNP rs12686676, in the NR4A3 gene locus encoding the nuclear receptor Nor-1. Nor-1 is expressed in β-cells, however, not much is known about its function with regard to insulin gene expression and insulin secretion.

The myocyte expression of adiponectin receptors and PPARδ is highly coordinated and reflects lipid metabolism of the human donors.

Muscle lipid oxidation is stimulated by peroxisome proliferator-activated receptor (PPAR) δ or adiponectin receptor signalling. We studied human myocyte expression of the PPARδ and adiponectin receptor genes and their relationship to lipid parameters of the donors. The mRNA levels of the three adiponectin receptors, AdipoR1, AdipoR2, and T-cadherin, were highly interrelated (r ≥ 0.

Inflammatory response of human coronary artery endothelial cells to saturated long-chain fatty acids.

Saturated long-chain fatty acids (SFAs) exert unfavourable metabolic effects (lipotoxicity) and induce apoptotic cell death (lipoapoptosis) in certain cell-types. Their contribution to inflammatory cell responses is unclear. We studied the expression of 113 inflammatory genes in human coronary artery endothelial cells (hCAECs) and their regulation by SFAs and unsaturated long-chain fatty acids (UFAs).

Muscle-derived angiopoietin-like protein 4 is induced by fatty acids via peroxisome proliferator-activated receptor (PPAR)-delta and is of metabolic relevance in humans.

Objective: Long-chain fatty acids (LCFAs) contribute to metabolic homeostasis in part via gene regulation. This study's objective was to identify novel LCFA target genes in human skeletal muscle cells (myotubes).

Research Design And Methods: In vitro methods included culture and treatment of human myotubes and C2C12 cells, gene array analysis, real-time RT-PCR, Western blotting, ELISA, chromatin immunoprecipitation, and RNA interference.

Effect of insulin detemir, compared to human insulin, on 3T3-L1 adipogenesis.

Insulin detemir (DET) represents a myristic acid (MA)-coupled insulin derivative with protracted action due to reversible albumin binding. As compared to human insulin (HI), DET provokes no or only minor body weight gain in vivo. Therefore, we compared DET's and HI's adipogenic effects.

Hypomagnesemia and nephrocalcinosis in a patient with two heterozygous mutations in the CLDN16 gene.

We report the case of a 20-year-old male Caucasian patient with diagnosed nephrocalcinosis and a medical history of seizures and recurrent urinary tract infections. Laboratory investigations revealed clinical and biochemical abnormalities characteristic of familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Since FHHNC is caused by mutations in the CLDN16 gene encoding a renal tight junction protein, we sequenced the complete coding region of this gene and detected two heterozygous mutations, the known Leu151Phe (+453G-->T) mutation and a novel Cys120Arg (+358T-->C) mutation.

Saturated, but not unsaturated, fatty acids induce apoptosis of human coronary artery endothelial cells via nuclear factor-kappaB activation.

High nonesterified fatty acid (NEFA) concentrations, as observed in the metabolic syndrome, trigger apoptosis of human umbilical vein endothelial cells. Since endothelial apoptosis may contribute to atherothrombosis, we studied the apoptotic susceptibility of human coronary artery endothelial cells (HCAECs) toward selected NEFAs and the underlying mechanisms. HCAECs were treated with single or combined NEFAs.