Serum and Adipose Tissue mRNA Levels of ATF3 and FNDC5/Irisin in Colorectal Cancer Patients With or Without Obesity

Objectives: To explore the activating transcription factor 3 (ATF3) and fibronectin type III domain-containing protein 5 (FNDC5)/irisin protein levels in serum and mRNA levels in subcutaneous and visceral white adipose tissue (sWAT and vWAT) in normal-weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC).Methods: 76 CRC patients and 40 healthy controls were recruited. Serum ATF3 and irisin levels were detected by using ELISA kits, and the mRNA expression levels in sWAT and vWAT were measured by performing RT-qPCR.Results: The serum ATF3 levels were greater by 37.2%, whereas the irisin levels were lower by 23.3% in NW+CRC patients compared with those in healthy controls. CRC was independently associated with both ATF3 and irisin levels. The probability of CRC greater by 22.3-fold in individuals with high ATF3 levels compared with those with low ATF3 levels, whereas the risk of CRC in subjects with high irisin levels was lower by 78.0% compared to the risk in those with low irisin levels after adjustment for age, gender, BMI, and other biochemical parameters. Serum ATF3 and irisin could differentiate CRC patients from controls with receiver operating characteristic (ROC) curve areas of 0.745 (95% CI, 0.655–0.823) and 0.656 (95% CI, 0.561–0.743), respectively. The combination of ATF3 and irisin exhibited improved diagnosis value accuracy with ROC curve areas of 0.796 (95% CI, 0.710–0.866) as well as 72.6% sensitivity and 80.0% specificity.Conclusion: Increased ATF3 and reduced irisin levels were observed in sera from CRC patients. Individuals with high ATF3 and low irisin levels were more likely to have CRC. ATF3 and irisin represent potential diagnostic biomarkers for CRC patients

Novel mechanisms for prevention and treatment of type 2 diabetes

Type 2 diabetes (T2D) is wereldwijd een van de meest voorkomende chronische ziektes geworden in de laatste 20-30 jaar. Alhoewel de ontdekking van insuline een gigantisch succes is in de geschiedenis van diabetes behandeling, moeten we nog verschillende problemen overkomen die insuline nog niet heeft opgelost. Daarnaast zijn er een aantal nieuwe problemen opgedoken als bijwerkingen van insuline gebruik zoals bijvoorbeeld insuline geïnduceerde hypoglycemie. Het cruciale probleem is dat we de chronische en vaak ernstige complicaties van T2D niet kunnen voorkomen en we ook ideale methode ter preventie van T2D ontwikkeling nog niet hebben gevonden. Het is van vitaal belang om nieuwe mechanismen van T2D te onderzoeken zodat we T2D effectiever kunnen bestrijden in de nabije toekomst. In dit proefschrift bekijk ik nieuwe mechanismen voor preventie en behandeling van T2D, en beschrijf ik een aantal studies naar nieuwe mechanismen vanuit verschillende perspectieven inclusief belangrijke bevindingen vanuit genetische studies. In hoofdstuk 1 geef ik een kort historisch overzicht van diabetes therapie sinds de introductie van insuline in de kliniek. Insuline heeft het leven van diabetes patiënten significant verlengd, maar het heeft klinische dokters en wetenschappers de mogelijkheid gegeven om de complicaties die gepaard gaan met chronische diabetes te observeren. Deze complicaties zijn tot op dit moment nog niet opgelost. Om T2D effectief te voorkomen en behandelen is er een dringende behoefte aan nieuwe medicijnen. Hiervoor is meer onderzoek nodig naar mechanismen die actief zijn in T2D, vooral vanuit de genetisch oogpunt. Insuline kan serieuze bijwerkingen veroorzaken, die, alhoewel niet zo frequent als eerder, nog steeds een probleem vormen. Om oplossingen te vinden voor deze problemen moeten we eerst de mechanismen die aan T2D ten grondslag liggen ontdekken en ze beter begrijpen. In Hoofdstuk 2 geef ik een overzicht van 50 loci geassocieerd met T2D die vooral ontdekt zijn door genoom-wijde associatie studies. De nieuw geïdentificeerde kandidaat genen zijn potentiële doelwitten van anti-diabetische medicijnen in de toekomst.

A Twin Study of Problematic Internet Use: Its Heritability and Genetic Association With Effortful Control

Our goal was to estimate genetic and environmental sources of influence on adolescent problematic internet use, and whether these individual differences can be explained by effortful control, an important aspect of self-regulation. A sample of 825 pairs of Chinese adolescent twins and their parents provided reports of problematic internet use and effortful control. Univariate analysis revealed that genetic factors explained 58-66% of variance in problematic internet use, with the rest explained by non-shared environmental factors. Sex difference was found, suggesting boys' problematic internet use was more influenced by genetic influences than girls' problematic internet use. Bivariate analysis indicated that effortful control accounted for a modest portion of the genetic and non-shared environmental variance in problematic internet use among girls. In contrast, among boys, effortful control explained between 6% (parent report) and 20% (self-report) of variance in problematic internet use through overlapping genetic pathways. Adolescent problematic internet use is heritable, and poor effortful control can partly explain adolescent problematic internet use, with effects stronger for boys. Implications for future research are discussed

Familial dysalbuminemic hyperthyroxinemia combined with Graves’ disease: a rare case report

Abstract Background Familial dysalbuminemic hyperthyroxinemia (FDH) is an autosomal dominant disease characterised by an abnormally increased affinity of albumin for serum thyroxine. Assay interference and differential diagnosis remain challenging for FDH. The condition is more complicated when FDH is combined with primary thyroid diseases. Co-occurrence of FDH and Graves’ disease is rare. Case presentation We report the case of a 28-year-old woman with complex FDH and coexisting Graves’ disease. Initially, the existence of FDH was not recognised. Graves’ disease was relieved after treatment with antithyroid drugs and two administrations of radioactive iodine therapy. She subsequently developed primary hypothyroidism and was prescribed levothyroxine replacement. However, thyroid function failed to normalise despite frequent levothyroxine dose adjustments. Ultimately, syndromes involving the inappropriate secretion of thyroid-stimulating hormone (IST) were considered, and FDH was successfully differentiated from other causes of IST. Conclusions A greater focus on FDH when investigating the causes of IST is critical to correctly evaluate thyroid function status and avoid inappropriate treatment, especially in complicated cases with concurrent FDH and primary thyroid diseases

Effects of vaspin on pancreatic β cell secretion via PI3K/Akt and NF-κB signaling pathways.

Vaspin (visceral adipose tissue-derived serine protease inhibitor) is a recently discovered adipokine that has been implicated in diabetes mellitus and other metabolic disorders. However, the effects of vaspin on pancreatic β cell function and related mechanisms are not fully understood. Thus, the present study was performed to investigate the effects of vaspin on pancreatic β cell function and the potential underlying mechanisms. Both in vitro (rat insulinoma cells, INS-1) and in vivo (high fat diet fed rats) experiments were conducted. The results showed that vaspin significantly increased INS-1 cell secretory function. Potential mechanisms were explored using inhibitors, western blot and real-time PCR techniques. We found that vaspin increased the levels of IRS-2 mRNA and IRS-2 total protein, while decreased the serine phosphorylation level of IRS-2 protein. Moreover, vaspin increased the Akt phosphorylation protein level which was reversed by PI3K inhibitor ly294002. In addition, vaspin increased the phosphorylation levels of mTOR and p70S6K, which was inhibited by rapamycin. Meanwhile, we found that the NF-κB mRNA and protein levels were reduced after vaspin treatment, similar to the effect of NF-κB inhibitor TPCK. Furthermore, vaspin increased the glucose stimulated insulin secretion (GSIS) level, lowered blood glucose level and improved the glucose tolerance and insulin sensitivity of high fat diet fed rats. Hyperglycemic clamp test manifested that vaspin improved islet β cell function. Together, these findings provide a new understanding of the function of vaspin on pancreatic β cell and suggest that it may serve as a potential agent for the prevention and treatment of type 2 diabetes

Are hypertriglyceridemia and low HDL causal factors in the development of insulin resistance?

Insulin resistance often occurs with dyslipidemia as part of the metabolic syndrome and the current dominant paradigm is that insulin resistance leads to dyslipidemia. However, dyslipidemia may also cause insulin resistance; this was postulated 30 years ago, but has never been substantiated. Establishing whether dyslipidemia plays a causal role in the etiology of insulin resistance is important since it could reveal new avenues for combating type 2 diabetes. In this review we summarize recent evidence from epidemiological, genetic and intervention studies to re-address this old hypothesis