Association of Serum Adiponectin Level with Dyslipidaemia in North Indian Male Population: A Case-control Study

Introduction: Adiponectin is the most abundant adipocytokines secreted from adipose tissues and circulates in considerably high concentration in human plasma. Circulating adiponectin levels are decreased in obese subjects and this decrease has been thought to play a crucial role in the early development of atherosclerosis and cardiovascular diseases. Changes in adiponectin concentration has been reported in dyslipidaemic subjects, but the evidence is controversial and no study has been conducted in north Indian population. Moreover, low molecular adiponectin seems to be linked with a worse lipid profile leading to dyslipidaemic through an association with triglyceride but the exact role of adiponectin in modulating lipid fraction is not well established. Aim: To correlate the level of serum adiponectin with lipid fractions in dyslipidaemic male subjects and also to compare them with apparently healthy individuals. Materials and Methods: This case-control study was conducted from April 2015 to November 2016 in the Biochemistry Department of Rajshree Medical Research Institute, Bareilly, Uttar Pradesh, India. A total of 70 non diabetic dyslipidaemic male subjects between the age group 35 years to 55 years were selected and all the biochemical parameters (adiponectin, fasting plasma glucose, lipid profile) were evaluated and compared with 70 apparently healthy controls. Statistical analysis was performed by licensed version of Statistical Package for Social Sciences (SPSS) 16.0 software. All the data were expressed in “mean±SD”. Student ‘t’ test was also applied to see statistical significance in adiponectin levels between dyslipidaemic subjects and healthy controls. Results: The study shows mean±SD of age in dyslipidaemic group was 43.61±4.85 years and for control group was 43.53±5.53 years. The mean±SD of BMI in dyslipidaemic group 25.72±2.43 was significantly higher than control group 23.42±1.56 with p-value <0.0001. The serum adiponectin concentration was significantly reduced in dyslipidaemic subjects 5.11±2.04 μg/mL as compared to healthy control 6.79±1.37 μg/mL with p-value <0.0001. Serum total cholesterol, triglyceride and Low Density Lipoprotein (LDL)- cholesterol were found to be negatively correlated with serum adiponectin (r= -0.89, -0.76 and -0.74) and positively correlated with High Density Lipoprotein (HDL)-cholesterol (r=0.70). Conclusion: The present study revealed that hypoadiponectinemia is associated with dyslipidaemic in men. The main observation of our present study, however, is that in dyslipidaemic subjects, lower levels of adiponectin were associated with high total cholesterol, triglyceride, LDL-cholesterol and reduced HDL cholesterol, though more extensive, multicentric, prospective research with increase sample size could obtain wider insights

A New Cell Secreting Insulin

The pancreatic �-cell is the only cell in animals that expresses the insulin gene and secretes insulin protein. We have found copious release of immunoreactive and bioactive insulin into the medium from the primary culture of carp adipocytes. Glucose augmented this release to more than 2-fold, and glucose transporter, Glut2, was detected in these cells. These all reflect characteristics of a pancreatic �-cell. The expression of the adipocyte-specific flotillin gene, the presence of peroxisomal proliferator-activated receptor � and Glut4, and the colocalization of insulin and leptin confirmed the identity of these cells as adipocytes. Purified carp adipocyte insulin (AdpInsl) comigrated with porcine and bovine insulin in SDSPAGE, indicating the similarity of their molecular sizes (5.5 kDa). AdpInsl strongly reduced hyperglycemia in streptozotocin- induced diabetic rats. It also stimulated significantly higher glucose uptake in carp and hamster adipocytes than porcine insulin. Adipocyte RNA hybridized with rat and zebrafish insulin cDNA showing the expression of the insulin gene in this cell. Using oligonucleotide primers designed on the basis of conserved insulin domain, AdpInsl cDNA was reverse transcribed, cloned, and sequenced. The deduced amino acid sequence of AdpInsl A and B chain exhibited 98% homology with zebrafish and more than 70% homology with human, porcine, and murine insulin. To understand the structurefunction relationship between AdpInsl and mammalian �-cell insulin, we have analyzed the amino acid sequences and three-dimensional structure of AdpInsl. In the critical determinant segment for receptor binding, AdpInsl has His at the A8 position instead of Thr in human and porcine insulin, and this attributed greater biological activity to AdpInsl. Our results show that carp adipocyte is a unique cell. As an insulin target cell it can express the insulin gene and secrete highly active insulin protein; thus, it may serve as a natural alternative to pancreatic �-cell insulin. (Endocrinology 144: 1585–1593, 200

Inhibition of Insulin Receptor Gene Expression and Insulin Signaling by Fatty Acid: Interplay of PKC Isoforms Therein

Fatty acids are known to play a key role in promoting the loss of insulin sensitivity causing insulin resistance and type 2 diabetes. However, underlying mechanism involved here is still unclear. Incubation of rat skeletal muscle cells with palmitate followed by I125- insulin binding to the plasma membrane receptor preparation demonstrated a two-fold decrease in receptor occupation. In searching the cause for this reduction, we found that palmitate inhibition of insulin receptor (IR) gene expression effecting reduced amount of IR protein in skeletal muscle cells. This was followed by the inhibition of insulin-stimulated IRβ tyrosine phosphorylation that consequently resulted inhibition of insulin receptor substrate 1 (IRS 1) and IRS 1 associated phosphatidylinositol-3 kinase (PI3 Kinase), phosphoinositide dependent kinase-1 (PDK 1) phosphorylation. PDK 1 dependent phosphorylation of PKCζ and Akt/PKB were also inhibited by palmitate. Surprisingly, although PKCε phosphorylation is PDK1 dependent, palmitate effected its constitutive phosphorylation independent of PDK1. Time kinetics study showed translocation of palmitate induced phosphorylated PKCε from cell membrane to nuclear region and its possible association with the inhibition of IR gene transcription. Our study suggests one of the pathways through which fatty acid can induce insulin resistance in skeletal muscle cell