In non-diabetic persons whose serum triglyceride (TG) concentrations ranged from normal to very high levels, endogenous TG turnover was measured using the radioglycerol method of Farquhar and coworkers. Insulin, FFA, and glucose concentrations were estimated during an oral glucose tolerance test. Stimulated insulin levels were correlated positively to TG concentrations and absolute TG turnover rates, and negatively to fractional TG catabolic rates. FFA concentrations had similar relationships, also in non-insulin-dependent diabetics. A more detailed analysis showed that elevated insulin and FFA levels - as an expression of peripheral insulin resistance - are typical finding in the kind of patients whose fractional TG catabolic rate is low [less than or equal to 0.210 (h-1)], irrespective of actual serum TG concentration. Our data do not suggest a stimulatory role of insulin for TG production.

Adult↗

PubMedDate not supplied

Urokinase-induced mitogenesis is mediated by casein kinase 2 and nucleolin.

BACKGROUND: Urokinase (uPA) and the urokinase receptor (uPAR) form a multifunctional system capable of concurrently regulating pericellular proteolysis, cell-surface adhesion, and mitogenesis. The role of uPA and uPAR in directed proteolysis is well established and its function in cellular adhesiveness has recently been clarified by numerous studies. The molecular mechanisms underlying the mitogenic effects of uPA and uPAR are still unclear, however. RESULTS: We identified mechanisms that might participate in uPA-related mitogenesis in human vascular smooth muscle cells and demonstrated that uPA induces activation of a unique signaling complex. This complex contains uPAR and two additional proteins, nucleolin and casein kinase 2, which are implicated in cell proliferation. Both proteins were isolated by affinity chromatography on uPA-conjugated cyanogen-bromide-activated Sepharose 4B and were identified using nano-electrospray mass spectrometry and immunoblotting. We used laser scanning and immunoelectron microscopy studies to further demonstrate that nucleolin and casein kinase 2 are located on the cell surface where they colocalize with the uPAR. Moreover, the proteins were co-internalized into the cell as an entire complex. Immunoprecipitation experiments in combination with an in vitro kinase assay demonstrated a specific association of uPAR with nucleolin and casein kinase 2 and revealed a uPA-induced activation of casein kinase 2, which presumably led to phosphorylation of nucleolin. Blockade of nucleolin and casein kinase 2 with specific modulators led to the inhibition of uPA-induced cell proliferation. CONCLUSIONS: We conclude that in human vascular smooth muscle cells, uPA induces the formation and activation of a newly identified signaling complex comprising uPAR, nucleolin, and casein kinase 2, that is responsible for the uPA-related mitogenic response. The complex is not a unique feature of vascular smooth muscle cells, as it was also found in other uPAR-expressing cell types.

Amino Acid Sequence↗

PubMedDate not supplied

Genetic roots of the red deer (Cervus elaphus) population in Eastern Switzerland.

Overhunting of red deer (Cervus elaphus) in eastern Switzerland led to its extinction in the second half of the 17th century. Natural recolonization must have taken place later, because red deer were seen again in the canton of the Grisons (eastern Switzerland) in the 1870s. According to historical data, three different populations could have served as the source population. To determine the genetic origin of the eastern Swiss red deer population, we collected samples from five different subpopulations in the canton of the Grisons as well as from four adjacent populations in Germany, Liechtenstein, Austria, and Italy. We analyzed the samples by genotyping 18 microsatellite loci. F(ST) values, assignment tests, correspondence analysis, and fuzzy clustering clearly pointed to Liechtenstein as the most probable source population for the red deer in eastern Switzerland. In addition, our analyses revealed high gene diversity in all examined populations. Gene flow and the high genetic admixture are discussed.

Animals↗