Role of GALNT2 on Insulin Sensitivity, Lipid Metabolism and Fat Homeostasis

O-linked glycosylation, the greatest form of post-translational modifications, plays a key role in regulating the majority of physiological processes. It is, therefore, not surprising that abnormal O-linked glycosylation has been related to several human diseases. Recently, GALNT2, which encodes the GalNAc-transferase 2 involved in the first step of O-linked glycosylation, has attracted great attention as a possible player in many highly prevalent human metabolic diseases, including atherogenic dyslipidemia, type 2 diabetes and obesity, all clustered on the common ground of insulin resistance. Data available both in human and animal models point to GALNT2 as a molecule that shapes the risk of the aforementioned abnormalities affecting diverse protein functions, which eventually cause clinically distinct phenotypes (a typical example of pleiotropism). Pathways linking GALNT2 to dyslipidemia and insulin resistance have been partly identified, while those for type 2 diabetes and obesity are yet to be understood. Here, we will provide a brief overview on the present knowledge on GALNT2 function and dysfunction and propose novel insights on the complex pathogenesis of the aforementioned metabolic diseases, which all impose a heavy burden for patients, their families and the entire society.

GLP-1a: Going Beyond Traditional Use

Glucagon-like peptide-1 (GLP-1) is a human incretin hormone derived from the proglucagon molecule. GLP-1 receptor agonists are frequently used to treat type 2 diabetes mellitus and obesity. However, the hormone affects the liver, pancreas, brain, fat cells, heart, and gastrointestinal tract. The objective of this study was to perform a systematic review on the use of GLP-1 other than in treating diabetes. PubMed, Cochrane, and Embase were searched, and the PRISMA guidelines were followed. Nineteen clinical studies were selected. The results showed that GLP-1 agonists can benefit defined off-medication motor scores in Parkinson’s Disease and improve emotional well-being. In Alzheimer’s disease, GLP-1 analogs can improve the brain’s glucose metabolism by improving glucose transport across the blood–brain barrier. In depression, the analogs can improve quality of life and depression scales. GLP-1 analogs can also have a role in treating chemical dependency, inhibiting dopaminergic release in the brain’s reward centers, decreasing withdrawal effects and relapses. These medications can also improve lipotoxicity by reducing visceral adiposity and decreasing liver fat deposition, reducing insulin resistance and the development of non-alcoholic fatty liver diseases. The adverse effects are primarily gastrointestinal. Therefore, GLP-1 analogs can benefit other conditions besides traditional diabetes and obesity uses.

Role of Pterostilbene in Metabolic Diseases through SIRT1 pathway- A Review

Pterostilbene (PTE) (3-5 dimethoxy-4-hydroxy-trans-stilbenes) is an analogue of resveratrol. It is extracted and isolated from a natural source of the heartwood of Pterocarpus marsupium Roxb., red grape skin, and blueberries (Vaccinium spp.). Substantial evidence suggested that PTE displayed numerous preventive and therapeutic properties in many metabolic disorders such as diabetes and obesity. Metabolic diseases result in Insulin resistance (IR) which advances to impaired sensitivity to insulin-mediated glucose disposal. The prominent role of SIRT (silent information regulator proteins) is now getting emphasized in metabolic disorders. SIRT1 represses Uncoupling protein 2 (UCP2) expressions which are further responsible for improving synthesis of ATP from glucose. This results in improving glucose utilization and insulin secretion, thus preventing IR. SIRT1 also exhibits prominent role in facilitating fatty acid mobilization thereby inhibiting adiposity. Metabolic disorders are therefore the consequences of SIRT1 downregulation. Pterostilbene, being a SIRT1 activator, increases insulin sensitivity reduces adiposity, therefore can prove to be beneficial in diabetes as well as obesity. The review summarizes therapeutic effects portrayed by Pterostilbene via the SIRT1 pathway in metabolic diseases.

Incidence and risk factors associated with development of oxalipatin-induced acute peripheral neuropathy in colorectal cancer patients

Introduction Oxaliplatin utilized in colorectal neoplasms treatment could induce acute peripheral neuropathy (APN) which is a dreadful and frequent adverse event. The objective of this study is to estimate incidence of APN induced by oxaliplatin cumulative incidence in cancer patients colorectal and to describe the distribution of the APN incidence according to demographic and clinical characteristics, as well as according to oxaliplatin cumulative dose. Material and methods This is a prospective descriptive study which took place from June to December 2018 at the Salah Azaiz Institute, Tunis. Demographic data, clinical data and data on oxaliplatin administration were collected from patient interview, medical files and pharmaceutical databases. Results The APN (grade 1, grade 2 and grade 3) cumulative incidence during the period of six months of follow up was 86% (95% CI [0.7815–0.9132]). While 38.3% (95% CI [0.29–0.48]) of the patients had grade 2 or 3 neuropathy. The search for factors associated with the risk of grade 2 and 3 NAP revealed trend significant association with diabetes (adjusted RR = 5.7 (IC95% [0.9- 37.3]; p = 0.07). Moreover, there was significant association with oxaliplatin cumulative dose (≥421 mg/m2) to increase the risk of APN grade 2 and 3 (adjusted RR = 7.8; [2.7–22.7]; p = 0.0001). Furthermore, significant association with obesity to increase the risk of APN grade 2 and 3 (adjusted RR = 5.3 [1.1- 25.4]; p = 0.04) was found. Among the patients included, 31.1% experienced oxaliplatin dose reduction and in the majority of cases this reduction is due to neurotoxicity (90.9%). Conclusion The high incidence of oxaliplatin-induced APN remains an embarrassing and handicapping side effect. Our study has shown that oxaliplatin cumulative dose (≥421 mg/m2), diabetes and obesity are risk factor for the development of grade 2 and 3 APN.