Correlation of CA 19-9 with HbA1c in prediabetic and diabetic groups

Introduction and Aim: Carbohydrate antigen19-9 (CA 19-9) is a marker of pancreatic cancer. In diabetics, pancreatic beta cell dysfunction can lead to elevated serum CA19-9 level. This study was designed for estimation of CA19-9 in diabetes and its correlation with glucose levels and glycosylated hemoglobin. Materials and Methods: The includes diabetic, pre diabetic with no history of malignancies and healthy normal subjects (n=50 each). Ca19-9 was estimated using ELISA, HbA1c by D10-Biorad variant turbo and the Lipid profile in Roche COBAs 6000 auto analyzer. Statistical analysis was done by Statistical Package for Social Sciences software version17 (SPSS 17). P <0.05 was considered significant. Results: Serum CA19-9 level was high in diabetics compared to normal, (p=0.38) however it was decreased in pre diabetic group (P=0.06). There was significant difference in comparison of CA19-9 levels between pre diabetic and diabetics(p=0.001). A significant increase in triglycerides was observed both in diabetics (p<0.01) and pre-diabetics(p=0.04). There was a significant positive correlation of CA19-9 with TC/HDL (p=0.022) and non-HDL(p) in control group. Conclusion: CA19-9 levels can be influenced by glycemic status, hence assessment of pancreatic cancer in diabetic patients must be interpreted carefully in consideration with CA19-9 levels. CA19-9 level was decreased in prediabetics when compared to normal and diabetics. This is a novel finding, the cause for which must ascertained, and this will open further avenues for research.

Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion

Over the last decades, lipotoxicity and glucotoxicity emerged as established mechanisms participating in the pathophysiology of obesity-related type 2 diabetes in general, and in the loss of β-cell function in particular. However, these terms hold various potential biological processes, and it is not clear what precisely they refer to and to what extent they might be clinically relevant. In this review, we discuss the basis and the last advances of research regarding the role of free fatty acids, their metabolic intracellular pathways, and receptor-mediated signaling related to glucose-stimulated insulin secretion, as well as lipid-induced β-cell dysfunction. We also describe the role of chronically elevated glucose, namely, glucotoxicity, which promotes failure and dedifferentiation of the β cell. Glucolipotoxicity combines deleterious effects of exposures to both high glucose and free fatty acids, supposedly provoking synergistic defects on the β cell. Nevertheless, recent studies have highlighted the glycerolipid/free fatty acid cycle as a protective pathway mediating active storage and recruitment of lipids. Finally, we discuss the putative correspondence of the loss of functional β cells in type 2 diabetes with a natural, although accelerated, aging process.

CHRONIC AEROBIC EXERCISE PREVENTS HIGH-FRUCTOSE DIET-INDUCED IMPAIRMENT IN BLOOD PRESSURE IN HEALTHY YOUNG ADULTS: A DOUBLE-BLIND, RANDOMIZED CLINICAL TRIAL

The purpose of the study was to verify the effect of 4 weeks of a high-fructose diet associated with aerobic training on the risk factors for cardiometabolic diseases. Twenty-one young adults were randomized into three groups: high-fructose diet (HFD: 1 g/kg body weight of fructose/day), high-glucose diet (HGD: 1 g/kg body weight of glucose/day), and high-fructose diet and exercise (HFDE: 1 g/kg body weight of fructose/day + 3 weekly 60-minute sessions of aerobic exercise). Before and after the 4 weeks of the intervention, blood samples were taken and flow-mediated dilatation, insulin resistance index, pancreatic beta cell functional capacity index, insulin sensitivity index, and 24-hour blood pressure were evaluated. HFD showed an increase in uric acid concentrations (p = 0.040), and HGD and HFDE groups showed no changes in this outcome between pre- and post-intervention; however, the HFDE group showed increased uric acid concentrations from the middle to the end of the intervention (p = 0.013). In addition, the HFD group showed increases in nocturnal systolic blood pressure (SBP) (p = 0.022) and nocturnal diastolic blood pressure (DBP) (p = 0.009). The HGD group exhibited decreases in nocturnal SBP (p = 0.028) and nocturnal DBP (p = 0.031), and the HFDE group showed a decrease in 24-hour SBP (p = 0.018). The consumption of 1 g/kg of fructose per day can increase uric acid concentrations and blood pressure in adults. Additionally, aerobic exercises along with fructose consumption attenuate changes in uric acid concentrations and prevent impairment in nocturnal blood pressure.

Islet primary cilia motility controls insulin secretion

Primary cilia are specialized cell-surface organelles that mediate sensory perception and, in contrast to motile cilia and flagella, are thought to lack motility function. Here we show that primary cilia in pancreatic beta cells exhibit movement that is required for glucose-dependent insulin secretion. Beta cell cilia contain motor proteins conserved from those found in classic motile cilia, and their 3D motion is dynein-driven and dependent on ATP and glucose metabolism. Inhibition of cilia motion blocks beta cell calcium influx and insulin secretion. Beta cells from humans with type 2 diabetes have altered expression of cilia motility genes. Our findings redefine primary cilia as dynamic structures possessing both sensory and motile function and establish that pancreatic beta cell cilia movement plays a critical role in controlling insulin secretion.

A novel disease mechanism leading to the expression of a disallowed gene in the pancreatic beta-cell identified by non-coding, regulatory mutations controlling HK1

Gene expression is tightly regulated with many genes exhibiting cell-specific silencing when their protein product would disrupt normal cellular function. This silencing is largely controlled by non-coding elements and their disruption might cause human disease. We performed gene-agnostic screening of the non-coding regions to discover new molecular causes of congenital hyperinsulinism. This identified 14 non-coding de novo mutations affecting a 42bp conserved region encompassed by a regulatory element in intron 2 of Hexokinase 1 (HK1), a pancreatic beta-cell disallowed gene. We demonstrated that these mutations resulted in expression of HK1 in the pancreatic beta-cells causing inappropriate insulin secretion and congenital hyperinsulinism. These mutations identify a regulatory region critical for cell-specific silencing. Importantly, this has revealed a new disease mechanism for non-coding mutations that cause inappropriate expression of a disallowed gene.

Preparation of O/W nano-emulsion containing nettle and fenugreek extract and cumin essential oil for evaluating antidiabetic properties

The oil-in-water (O/W) nano-emulsion (NE) is expanded to enhance the bioavailability of hydrophobic compounds. The NE can be prepared by herbal extract and essential oil as herbal medicines for antidiabetic treatment. In the present study, the O/W NE was prepared by fenugreek extract (FE), nettle extract (NE), and cumin essential oil (CEO) using tween 80 and span 80 surfactants in an ultrasonic bath, at room temperature within 18 min. The antidiabetic property was evaluated by determining glucose absorption using cultured rat L6 myoblast cell line (L6) myotubes and insulin secretion using the cultured mouse pancreatic beta-cell (RIN-5) for NEs. The samples were investigated by dynamic light scattering (DLS) to examine the size distribution and size, zeta potential for the charge determination, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) to investigate morphology and size. The rheological properties were studied by viscosity. The sample stability was evaluated at different temperatures and days by DLS and SEM analyses. The cytotoxicity of samples was explored by MTT assay for HEK293 human cell line as a specific cell line originally derived from human embryonic kidney cells at three different concentrations for three periods of time. The NEs with nanometer-size were observed with antidiabetic properties, low cytotoxicity, and suitable stability. This study provides definitive evidence for the NE as a plant medicine with antidiabetic properties. The NE can be a good candidate for biomedical applications.