Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of Humans With Type 2 Diabetes

We have screened a subtracted cDNA library in order to identify differentially expressed genes in omental adipose tissue of human patients with Type 2 diabetes. One clone (#1738) showed a marked reduction in omental adipose tissue from patients with Type 2 diabetes. Sequencing and BLAST analysis revealed clone #1738 was the adipocyte-specific secreted protein gene apM1 (synonyms ACRP30, AdipoQ, GBP28). Consistent with the murine orthologue, apM1 mRNA was expressed in cultured human adipocytes and not in preadipocytes. Using RT-PCR we confirmed that apM1 mRNA levels were significantly reduced in omental adipose tissue of obese patients with Type 2 diabetes compared with lean and obese normoglycemic subjects. Although less pronounced, apM1 mRNA levels were reduced in subcutaneous adipose tissue of Type 2 diabetic patients. Whereas the biological function of apM1 is presently unknown, the tissue specific expression, structural similarities to TNFα and the dysregulated expression observed in obese Type 2 diabetic patients suggest that this factor may play a role in the pathogenesis of insulin resistance and Type 2 diabetes

Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 reduces bacterial translocation in rats treated with carbon tetrachloride

Probiotics can prevent pathological bacterial translocation by modulating intestinal microbiota and improving the gut barrier. The aim was to evaluate the effect of a fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 on bacterial translocation in rats with carbon tetrachloride (CCl)-induced cirrhosis. Sprague-Dawley rats treated with CCl were randomized into a probiotic group that received fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 in drinking water or a water group that received water only. Laparotomy was performed one week after ascites development. We evaluated bacterial translocation, intestinal microbiota, the intestinal barrier and cytokines in mesenteric lymph nodes and serum. Bacterial translocation decreased and gut dysbiosis improved in the probiotic group compared to the water group. The ileal β-defensin-1 concentration was higher and ileal malondialdehyde levels were lower in the probiotic group than in water group. There were no differences between groups in serum cytokines but TNF-α levels in mesenteric lymph nodes were lower in the probiotic group than in the water group. Fermented milk containing Lactobacillus paracasei subsp. paracasei CNCM I-1518 decreases bacterial translocation, gut dysbiosis and ileal oxidative damage and increases ileal β-defensin-1 expression in rats treated with CCl, suggesting an improvement in the intestinal barrier integrity

Low mitochondrial glycerophosphate dehydrogenase activity in lymphocytes of women with gestational diabetes

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Acarbose treatment or islet transplantation increase FAD-glycerophosphate dehydrogenase content in islets of diabetic rats

Male adult rats injected with streptozotocin during the neonatal period (STZ rats) showed low body weight, high fluid intake, increased glycaemia, low plasma insulin concentration, decreased islet content in FAD-glycerophosphate dehydrogenase (mGDH), low activity of mGDH in islet homogenates, low islet insulin content and decreased secretory responsiveness of the islets to D-glucose, as compared to control animals of same sex and age. When the STZ rats were given access to acarbose (40 mg/100 g of food) for one month, the fluid intake, glycaemia, pancreatic islet content in mGDH and activity of this enzyme in islet homogenates were all improved, but the plasma insulin concentration remained unchanged. Likewise, when the STZ rats were grafted with 1000-1200 islets from normal rats, the mGDH content of pancreatic islets again increased. This now coincided with a significant increase in plasma insulin concentration, but a somewhat lower increment (Δ) in insulin output, in response to a rise in D-glucose concentration from 2.8 to 16.7 mmol/l, in the islets from transplanted rats (Δ = 21.4 ± 6.2 μU/islet per 90 min) than in those from untreated STZ rats (Δ = 39.5 ± 8.8 μU/islet per 90 min). By comparison with data obtained in other experimental models of B-cell dysfunction, these findings suggest that sustained hyperglycaemia unfavourably affects expression of the mGDH gene in pancreatic islets of animals suffering from a primary alteration of their insulin-secreting cell population.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Sodium tungstate decreases the phosphorylation of tau through GSK3 inactivation

Tungstate treatment increases the phosphorylation of glycogen synthase kinase-3β (GSK3β) at serine 9, which triggers its inactivation both in cultured neural cells and in vivo. GSK3 phosphorylation is dependent on the activation of extracellular signal-regulated kinases 1/2 (ERK1/2) induced by tungstate. As a consequence of GSK3 inactivation, the phosphorylation of several GSK3-dependent sites of the microtubule-associated protein tau decreases. Tungstate reduces tau phosphorylation only in primed sequences, namely, those prephosphorylated by other kinases before GSK3β modification, which are serines 198, 199, or 202 and threonine 231. The phosphorylation at these sites is involved in reduction of the interaction of tau with microtubules that occurs in Alzheimer's disease.This work was supported by grants from the Spanish CICYT (SAF2003-02697 to J.A., SAF2004-06962 to J.J.G., SAF2003-06018 to R.G.), grants from the Spanish Ministry of Health (C03/08 to J.J.G., G03/212 to R.G.), and an institutional grant to CBMSO from the “Fundación R. Areces.”Peer reviewe

Inhibition of GSK3 dependent tau phosphorylation by metals

One of the main pathological characteristics of Alzheimers disease is the presence in the brain of the patients of an aberrant structure, the paired helical filaments, composed of hyperphosphorylated tau. The level of tau phosphorylation has been correlated with the capacity for tau aggregation. Thus, the mechanism for tau phosphorylation could be important to clarify those pathological features in Alzheimers disease. Tau protein could be modified by different kinases, being GSK3 the one that could modify more sites of that protein. GSK3 activity could be modulate by the presence of metals like magnesium that can be required for the proper function of the kinase, whereas, metals like manganesum or lithium inhibit the activity of the kinase. Many works have been done to study the inhibition of GSK3 by lithium, a specific inhibitor of that kinase. More recently, it has been indicated that sodium tungstate could also inhibit GSK3 through a different mechanism. In this review, we discuss the effect of these two metals, lithium and tungstate, on GSK3 (or tau I kinase) activity.This work was supported by grants from the Spanish and CICYT: SAF2003-02697 to JA; SAF2004-06962 to JJG; SAF2003-06018 to RG; from the Spanish Ministry of Health C03/08 to JJG; G03/212 to RG; FIS 04/0607 to JA; and an institutional grant to CBMSO from the “Fundación R. Areces”.Peer reviewe