空腹血糖受损患者脂联素水平的临床观察

目的探讨空腹血糖受损（IFG）患者脂联素水平的变化。方法入选糖耐量正常（NGT）、孤立性空腹血糖受损（I-IFG）、孤立性糖耐量低减（I-IGT）、空腹血糖受损并糖耐量低减（IFG／IGT）、新发2型糖尿病（T2DM）各30例，采用酶联免疫吸附法（ELISA）测定血清脂联素，同时检测胰岛素水平及血糖、血脂，计算胰岛素抵抗指数（HOMA．IR）。结果I-IFG组、1-IGT组、IFG／IGT组及新发T2DM组脂联素均明显低于NGT组（P均〈0．01）；新发T2DM组和IFG／IGT组的HOMA-IR均〉I-IGT组〉I-IFG组〉NGT组，各组间差异有统计学意义（P均〈0．05或P〈0．01）；脂联素与空腹血糖（FBG）、餐后2h血糖（2HBG）及HOMA-IR呈负相关（Pa〈0．01）。结论在I-IFG阶段已存在脂联素水平降低，胰岛素抵抗增加，具有向糖尿病转化及并发大血管病变的风险，提高脂联素水平可为糖尿病及其并发症的防治提供一条新的思路。     

miR-375 enhances palmitate-induced lipoapoptosis in insulin-secreting NIT-1 cells by repressing myotrophin (V1) protein expression

Lipoapoptosis of pancreatic β cells caused by elevated circulating free fatty acids (FFAs) has now been recognized to be a pivotal factor contributing to β cellular dysfunction and β-mass lose in type 2 diabetes. Although recent studies suggested an important role for the ceramide pathway in the late destructive phase of lipid overload in the pancreatic β cells, the overall underlying mechanisms leading to lipoapoptosis, however, remained poorly understood. mir-375 was recently characterized to be a pancreatic islet-specific miRNA implicated in the regulation of insulin secretion and β-mass turnover. In the present study we further examined its effect on palmitate-induced lipoapoptosis in NIT-1 cells, a NOD-derived β-cell line. It was found that NIT-1 cells with ectopic mir-375 expression were much more susceptible to palmitate-induced lipoapoptosis. In contrast, knockdown of endogenous pri-mir-375 expression by a modified antisense oligo, 2''-O-me-375, almost completely protected NIT-1 cells from palmitate-induced lipoapoptosis. We further demonstrated that mir-375 could target V1 mRNA and repress its translation. Consistent with this assumption, NIT-1 cells transfected with 2''-O-me-375 showed significant higher levels of V1 protein after palmitate induction. Together, our data suggest that mir-375 could be a potential therapeutic target for prevention and intervention of β-cell dysfunction and β-mass lose in type 2 diabetes.     

Density of γ/δ+ T cells in the jejunal epithelium of patients with coeliac disease and dermatitis herpetiformis is increased with age

Increased density of γ/δ T cell receptor (TCR)⁺ intraepithelial lymphocytes is the only characteristic in the jejunum of patients with coeliac disease and dermatitis herpetiformis which is not normalized on a gluten-free diet. We explored the age-dependent changes in intraepithelial γ/δ and α/β TCR⁺ cells from 137 biopsies from patients with coeliac disease and dermatitis herpetiformis and from controls. Biopsy specimens from 100 patients with coeliac disease and dermatitis herpetiformis and from 37 controls were studied with an immunohistochemical method using MoAbs to T cell receptors and peroxidase staining. An increase in the density of intraepithelial γ/δ T cells above the mean +2 s.d. of the density in controls was present in 97 of 100 specimens from patients with coeliac disease and dermatitis herpetiformis. The density of γ/δ⁺ cells of patients with coeliac disease and dermatitis herpetiformis on a normal gluten-containing diet showed a positive correlation with age (r = 0.45, P< 0.0001). In controls, the density of γ/δ⁺ cells remained low throughout the age-range studies, from age 0.6–57 years. In controls, α/β⁺ cells increased with age (r = 0.57, P< 0.001). The increase in density of intraepithelial lymphocytes with age is in agreement with their thymus-independent character and local proliferation.     

Increased serum insulin-like growth factor-1 levels in women with gestational diabetes

BackgroundInsulin-like growth factor-1 (IGF-1), which has effects similar to insulin, reduces blood glucose level, improves insulin sensitivity and may play an important role in the pathogenesis of gestational diabetes (GDM).ObjectiveThe aim of the study was to estimate the concentration of IGF-1 in pregnant women with GDM and 3 months after delivery and find relationships between IGF-1 and clinical and biochemical parameters.Materials and methods67 women between 24th - 28th week of pregnancy were enrolled in the study (46 with GDM and 21 as a control group). All women underwent clinical and biochemical examinations. Concentrations of IGF-1, adiponectin, fasting glucose, insulin, lipids, CRP, fibrinogen were measured during pregnancy, additionally IGF-1 concentration was determined 3 months after delivery.ResultsIGF-1, glucose, insulin, CRP, fibrinogen, lipids concentrations and HOMA-IR were significantly higher in women with GDM than in the control group (p<0.05). A significant decrease in IGF-1 concentration was observed in both groups after delivery. In the GDM group significant correlations between IGF-1 and BMI (r=0.370, p<0.05), insulin (r=0.469, p<0.01) and HOMA-IR (r=0.439, p<0.01) were observed. Regression analysis with IGF-1 as a dependent parameter showed that only BMI and insulin remained as predictors, explaining 32% of plasma IGF-1 variation. Re-evaluation after delivery revealed impaired glucose tolerance in 9% of the population studied.ConclusionsIncreased IGF-1 concentrations in pregnancy complicated with GDM may partly reflect metabolic disturbances, especially insulin resistance and hyperinsulinemia, and may be one of possible compensatory reactions of the organism in response to these disturbances.     

Effect of common single nucleotide polymorphisms in COX-1 gene on related metabolic activity in diabetic patients treated with acetylsalicylic acid

Introduction

The objective of this study was to investigate the effect of common single nucleotide genomic polymorphisms in the cyclooxygenase-1 (COX-1) gene on the thromboxane A₂ (TxA₂) metabolite concentrations in serum and urine, as well as on prostaglandin F2α (PGF2α) urinary excretion in the diabetic population on acetylsalicylic acid (ASA) therapy.

Material and methods

The study cohort consisted of 284 Caucasians with diabetes type 2 who had been taking ASA tablets at the dose of 75 mg/day for at least 3 months. Genotyping for the 4 selected SNPs within the COX-1 gene (two nonsynonymous-coding variants, rs3842787 [C50T, P17L] and rs5789 [C174A, L237M]; and two other synonymous SNPs, rs3842788 [G128A, Q41Q] and rs5788 [C644A]) was performed using the Sequenom iPLEX platform.

Results

No statistically significant results were observed for the investigated SNPs and measured metabolites in the investigated cohort of patients. Statistically significant differences in S-TxB₂ could however be observed for rs5788 in the subgroup of patients with very high S-TxB₂ concentrations. In particular, more patients who were carriers of the minor allele for this polymorphism were observed in the group with S-TxB₂ levels > 95^th percentile, when compared with similar carriers in the group with S-TxB₂ < 95^th percentile (20% vs. 1.1%, respectively, p < 0.001, Mann-Whitney test).

Conclusions

The results of our study suggest that the four investigated common SNPs in the COX1 gene are not associated with obviously altered TxA₂ metabolism and PGF2α synthesis in the investigated diabetic cohort treated with ASA.     

Culture of K562 human myeloid leukemia cells in presence of fibronectin expresses and secretes MMP-9 in serum-free culture medium

The interaction of cells with adhesion proteins in the extracellular matrix (ECM) provides signals which affect the morphology, motility, gene expression and survival of adherent cells. In the present communication we cultured K562 cells in presence of fibronectin to study the fibronectin-integrin mediated signalling and modulation of MMP expression. Our experimental findings demonstrate that exposure of K562 cells in serum free medium in presence of fibronectin up-regulates the expression of pro-MMP-9 within 2 hrs. Phosphorylation of focal adhesion kinase (FAK), ERK, PI-3K and nuclear translocation of EGFR and NF-kB upon FN binding demonstrate possible involvement of FAK/PI-3K/ERK signalling pathways in the fibronectin-integrin mediated up regulation of MMP-9 expression.     

Effect of glucagon on insulin secretion through cAMP signaling pathway in MIN6 cells

Objective: To explore the direct regulation effects and mechanisms of glucagon in insulin secretion of MIN6 cells that in the kind of the islet β cells. Methods ICUE3 and PCDNA3.1 plasmid were transfected to the MIN6 cells by electroporation transfection, and then treated with different concentrations of glucagon (Glg) and glucose (Glu). Biosensor technology that based on the fluorescence resonance energy transfer (FRET) was used to monitor the change of cAMP quantitatively and real-time. The level of cAMP and insulin were measured by the enzyme-linked immunosorbent assay (ELISA). Results: The receptor of Glg was mainly located on the cell membrane in MIN6 cells. Compared with the 0 ng/L Glg group in the Glu-free state, the average value of CFP/YFP increased 4% ± 0.02 in the 500 ng/L Glg group, and the value in the 1000 ng/L Glg group increased 6% ± 0.03 (P > 0.05). While in the high-Glu (16.7 mmol/L) state, the value increased 11% ± 0.02 in the 500 ng/L Glg group, and increased 23% ± 0.06 in the 1000 ng/L Glg group when compared with the 0 ng/L Glg group(P < 0.01). The levels of the cAMP of 1000 ng/L and 500 ng/L Glg group were higher than those of the 100 ng/L and 0 ng/L Glg group in the condition of Glu-free (81.27±6.29, 76.73±2.10,39.45±2.83, 40.36±4.20; P < 0.01). The levels of the cAMP of 1000 ng/L, 500 ng/L and 100 ng/L Glg group were higher than those of the 0 ng/L Glg group, at the meanwhile, the levels of the cAMP of 1000 ng/L and 500 ng/L Glg group were also higher than 100 ng/L Glg group in the condition of low-Glu (2.8 mmol/L) (92.91±7.35, 90.36±3.15, 65.82±10.49, 46.73±1.05; P < 0.01). And this trend in the condition of high-Glu was almost to the low-Glu (106.75±7.26, 94.18±2.99, 83.09±1.16, 55.60±5.51, P < 0.01). The levels of the insulin of 1000 ng/L, 500 ng/L and 100 ng/L Glg group were higher than those of the 0 ng/L Glg group. While 1000 ng/L Glg group was higher than that of the 500 ng/L and 100 ng/L Glg group in the condition of Glu-free (1844.02±200.93, 1387.94±483.12, 1251.817±60.30, 787.33±81.72; P < 0.01). The levels of the insulin of 1000 ng/L and 500 ng/L Glg group were higher than those of the 100 ng/L and 0 ng/L Glg group, and the 1000 ng/L and was also higher than 500 ng/L Glg group in the condition of low-Glu (1552.31±81.20, 1285.62±131.67, 1020.85±42.60, 762.89±26.94, P < 0.01). And this trend in the condition of high-Glu was almost to the low-Glu (1898.337±169.03, 1399.30±148.66, 1061.735±9.13, 972.89±22.19; P < 0.01). The levels of cAMP and insulin secretion of MIN6 cells had a positive correlation in different Glu conditions (r² = 0.559, P < 0.01). Conclusion: Glg may stimulate insulin secretion by increasing cAMP levels in the way of concentration gradient within the islet β cell lines--MIN6 cells. And the increasing trend was Glu dependent.     

Inverted Vδ1/Vδ2 ratio within the T cell receptor (TCR)-γδ T cell population in peripheral blood of heart transplant recipients

We investigated the levels of TCR-γδ T cells and their subpopulations Vδ1 and Vδ2 in the peripheral blood lymphocytes (PBL) of 28 heart transplant (HTx) patients. Patients (n = 10) receiving cyclosporin A (CsA) for treatment of a nephrotic syndrome (NS) and 10 healthy individuals served as controls. There was no difference in levels of TCR-γδ T cells between the different groups. However, an elevated proportion of Vδ1⁺γδ T cells was found in the PBL of HTx patients, especially when these cells were present in their graft-infiltrating lymphocyte (GIL) cultures. Vδ1⁺γδ T cells of HTx patients showed normal expression of CD45RO and lacked the activation markers CD25 and HLA-DR. After expanding in IL-2-containing medium, PBL cultures of HTx patients more often were dominated by Vδ1 cells than PBL cultures of controls, in which Vδ2 cells were predominantly grown. The aberrant composition of the TCR-γδ population in HTx patients was not a result of immunosuppressive medication, since the proportion Vδ1⁺γδ T cells was normal in the PBL of the NS patients receiving a similar dose of CsA. It is postulated that long-term antigenic stimulation by the graft, at low level, might be responsible for the altered composition of the γδ pool in the HTx patients. Since no donor HLA-specific γδ T cells have been detected, other ligands, such as heat shock proteins, may be involved.     

Dual therapy of rosiglitazone/pioglitazone with glimepiride on diabetic nephropathy in experimentally induced type 2 diabetes rats

Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (90 mg/kg) in neonatal rats and then these rats were treated with rosiglitazone (1.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-a signaling during the development of streptozotocin induced type 2 diabetic nephropathy.     

Pyruvate kinase,muscle isoform 2 promotes proliferation and insulin secretion of pancreatic β-cells via activating Wnt/CTNNB1 signaling

Failure of pancreatic β-cells is closely associated with type 2 diabetes mellitus (T2DM), an intractable disease affecting numerous patients. Pyruvate kinase, muscle isoform 2 (PKM2) is a potential modulator of insulin secretion in β-cells. This study aims at revealing roles and possible mechanisms of PKM2 in pancreatic β-cells. Mouse pancreatic β-cell line NIT-1 was used for high glucose treatment and PKM2 overexpression by its specific expression vector. Cell proliferation by Thiazolyl blue assay, cell apoptosis by annexin V-fluorescein isothiocyanate/prodium iodide staining and insulin secretion assay by ELISA were performed in each group. The mRNA and protein levels of related factors were analyzed by real-time quantitative PCR and western blot. Results showed that Pkm2 was inhibited under high glucose conditions compared to the untreated cells (P < 0.01). Its overexpression significantly suppressed NIT-1 cell apoptosis (P < 0.01), and induced cell proliferation (P < 0.05) and insulin secretion (P < 0.05). Related factors showed consistent mRNA expression changes. Protein levels of β-catenin (CTNNB1), insulin receptor substrate 1 (IRS1) and IRS2 were all promoted by PKM2 overexpression (P < 0.01), indicating the activated Wnt/CTNNB1 signaling. These results indicated the inductive roles of PKM2 in pancreatic β-cell NIT-1, including promoting cell proliferation and insulin secretion, and inhibiting cell apoptosis, which might be achieved via activating the Wnt/CTNNB1 signaling and downstream factors. This study offers basic information on the role and mechanism of PKM2 in pancreatic β-cells, and lays the foundation for using PKM2 as a potential therapeutic target in T2DM.     

Ultrastructural Localization of Insulin-like Growth Factor-2 (IGF-2) to the Secretory Granules of Insulin Cells: A Study in Normal and Diabetic (GK) Rats

By using biochemical and light-microscopical techniques, insulin-like growth factor-2 (IGF-2) has recently been found in adult pancreas, co-localized immunohistochemically with insulin in the islet B-cells. The purpose of this study was to trace IGF-2 immunoreactivity (IR) at the ultrastructural level in normal and diabetic Goto-Kakizaki (GK) rats. Using a pre-embed-ding technique and immuno-gold-silver staining, IGF-2 antibody binding was localized exclusively to the halo of a subset of secretory β-granules in normal rats. Insulin IR occurred more frequently in the granules. GK rats had, in addition to normal-looking islets, some islets with irregular shape and an increased amount of fibrous tissue, so-called “starfish-shaped” islets. In these, β-granules were usually found, but most of the B-cells were also occupied by large, usually electron-translucent vesicles, some resembling crinophagic bodies, i.e., the sign of intracellular degradation of secretory granules. In starfish-shaped islets, IGF-2 IR was localized to the halo of β-granules, as in GK islets with normal appearance. Occasionally, IGF-2 IR was also found in the cytoplasm and even in adjacent fibroblasts. Insulin IR was restricted to β-granules. Because the lysosomes have IGF-2 receptors, the presence of IGF-2 peptide in secretory granules could explain why some granules are guided to lysosomes for degradation.     

2型糖尿病患者红细胞免疫功能与血糖、胰岛素水平的相关性探讨

目的 :探讨了 2型糖尿病患者红细胞免疫功能的变化及其与血糖和胰岛素的相关性。方法 :应用免疫法测定 5 2例 2型糖尿病患者红细胞免疫功能 ,酶法测定血糖 ,放免法测定胰岛素含量并与 35名正常人作对照。结果 :2型糖尿病患者RBC -C3bRR水平明显降低 (p <0 0 1)与血糖和胰岛素水平呈负相关 (r=-0 32 5 1、- 0 3312 ,p<0 0 5 ) ,RBC -ICRRR水平明显高于正常人 (p <0 0 1) ,与血糖和胰岛素水平呈正相关 (r=0 35 12、0 346 4 ,p <0 0 5 )。结论 :2型糖尿病患者存在有红细胞免疫调节的紊乱 ,其免疫功能的低下与血糖和胰岛素升高有相关性。     

Adjuvant-Induced Improvement of Glucose Intolerance in Type 2 Diabetic KK-Ay Mice Through Interleukin-1 and Tumor Necrosis Factor-α

We reported that administration of complete Freund's adjuvant (CFA) improved glucose tolerance test (GTT) results in obese diabetic KK-Ay mice. In this study, we investigated its mechanism. An injection with CFA remarkably improved GTT for more than a week in KK-Ay mice, although insulin response was not changed compared with saline controls. The hypoglycemic effect of insulin was significantly, but partially, potentiated in the CFA-treated mice compared with the controls, suggesting that CFA stimulated insulin-mediated and non-insulin-mediated glucose disposal. Improvement in the GTT with CFA was partially transferable to nontreated mice by peritoneal exudative cells, but not spleen or lymph node cells. Pretreatment with anti-interleukin (IL)-1α and -1β antibodies or anti-tumor necrosis factor (TNF)-α antibody significantly abrogated the improvement in the GTT with CFA. The results indicate that CFA-induced improvement in glucose intolerance in KK-Ay mice was mediated at least by IL-1 and TNF-α.     

Impaired maturation and function of dendritic cells by mycobacteria through IL-1beta

Dendritic cells (DC) are pivotal for initiation and regulation of innate and adaptive immune responses evoked by vaccination and natural infection. After infection, mycobacterial pathogens first encounter monocytes, which produce pro-inflammatory cytokines, including IL-1beta, TNF-alpha and IL-6. The role of these cytokines in DC maturation remains incompletely understood. Here, we show that maturation of DC from monocytes was impaired by pretreatment of monocytes with low doses of IL-1beta. Under these conditions, Mycobacterium leprae-infected DC failed to stimulate antigen-specific T cell responses. Expression of CD86 and CD83 and production of IL-12 in response to lipopolysaccharide and peptidoglycan were diminished. In contrast, these DC functions were not impaired by pretreatment with TNF-alpha, IL-6 or IL-10. When monocytes were infected with M. bovis Bacillus Calmette-Guérin, and subsequently differentiated to DC, the activity of these DC was suppressed as well. Thus, IL-1beta acts at early stages of differentiation of DC and impairs biological functions of DC at later stages. Therefore, production of IL-1beta by mycobacteria-infected antigen-presenting cells counteracts effective stimulation of innate and adaptive immune responses.     

Phactr4 regulates directional migration of enteric neural crest through PP1, integrin signaling, and cofilin activity

Hirschsprung disease (HSCR) is caused by a reduction of enteric neural crest cells (ENCCs) in the gut and gastrointestinal blockage. Knowledge of the genetics underlying HSCR is incomplete, particularly genes that control cellular behaviors of ENCC migration. Here we report a novel regulator of ENCC migration in mice. Disruption of the Phactr4 gene causes an embryonic gastrointestinal defect due to colon hypoganglionosis, which resembles human HSCR. Time-lapse imaging of ENCCs within the embryonic gut demonstrates a collective cell migration defect. Mutant ENCCs show undirected cellular protrusions and disrupted directional and chain migration. Phactr4 acts cell-autonomously in ENCCs and colocalizes with integrin and cofilin at cell protrusions. Mechanistically, we show that Phactr4 negatively regulates integrin signaling through the RHO/ROCK pathway and coordinates protein phosphatase 1 (PP1) with cofilin activity to regulate cytoskeletal dynamics. Strikingly, lamellipodia formation and in vivo ENCC chain migration defects are rescued by inhibition of ROCK or integrin function. Our results demonstrate a previously unknown pathway in ENCC collective migration in vivo and provide new candidate genes for human genetic studies of HSCR.     

Workshop cluster 1+ gammadelta T-cell receptor T cells from calves express high levels of interferon-gamma in response to stimulation with interleukin-12 and -18

Gammadelta T-cell receptor(+) T lymphocytes are an important element of the innate immune system. Early production of interferon (IFN)-gamma by gammadelta T cells may have a role in linking innate and adaptive immune responses and contribute to T helper-1 bias. We investigated the role of cytokines in the activation and induction of IFN-gamma secretion by bovine workshop cluster 1(+) (WC1(+)) gammadelta T cells. The effects of culture with interleukin (IL)-12, IL-18, IL-15 and IL-2 were investigated; these cytokines are known to influence murine and human gammadelta T cells. We report that bovine WC1(+)gammadelta T cells are synergistically stimulated by IL-12 and IL-18 to secrete large quantities of IFN-gamma. Neonatal calves were shown to have significantly higher numbers of circulating WC1(+)gammadelta T cells than adult animals. In addition, the response of peripheral blood WC1(+)gammadelta T cells was significantly higher in neonatal calves compared with adult animals. However, in adult animals the response of lymph node WC1(+)gammadelta T cells to IL-12/IL-18 was more pronounced than that of peripheral blood WC1(+)gammadelta T cells. We hypothesize that the induction of IFN-gamma secretion from WC1(+)gammadelta T cells by IL-12 and IL-18 is likely to be an important element of the innate response to pathogens such as Mycobacterium bovis. The high numbers of WC1(+)gammadelta T cells in neonatal calves, and their inherent ability to respond to inflammatory cytokines, could be a key factor in the enhanced responses seen in calves to BCG vaccination.     

First outbreak of multidrug-resistant Klebsiella pneumoniae producing both SHV-12-type extended-spectrum beta-lactamase and DHA-1-type AmpC beta-lactamase at a Korean hospital

PURPOSE: Coexistence of different classes of beta-lactamases in a single bacterial isolate may pose diagnostic and therapeutic challenges. We investigated a spread of Klebsiella pneumoniae isolates co-producing an AmpC beta-lactamase and an extended-spectrum beta-lactamase (ESBL) in a university hospital. MATERIALS AND METHODS: Over a three-month period, a total of 11 K. pneumoniae isolates, which exhibited resistance to cefotaxime, aztreonam, and cefoxitin, were isolated. These isolates showed positive to ESBLs by double disk tests. Minimal inhibitory concentrations (MICs) were determined by broth microdilution testing. All isolates were examined by isoelectric focusing, PCR and sequence analysis to identify bla(SHV) and bla(DHA), and molecular typing by pulsed-field gel electrophoresis (PFGE). RESULTS: All 11 isolates were highly resistant (MIC, > or = 128microg/ml) to ceftazidime, aztreonam, and cefoxitin, while they were susceptible (MIC, < or = 2microg/ml) to imipenem. The bla(SHV-12) and bla(DHA-1) genes were detected by PCR and sequence analysis. PFGE revealed a similar pattern in 10 of the 11 strains tested. CONCLUSION: This is the first outbreak report of K. pneumoniae in Korea which co-produced SHV-12 and DHA-1 beta-lactamase, and we suggest a clonal spread of multidrug-resistant K. pneumoniae at a hospital.     

Genetic analysis of the ELOVL6 gene polymorphism associated with type 2 diabetes mellitus

Recent animal studies have indicated that overexpression of the elongation of long-chain fatty acids family member 6 (Elovl6) gene can cause insulin resistance and β-cell dysfunction. These are the major factors involved in the development of type 2 diabetes mellitus (T2DM). To identify the relationship between single nucleotide polymorphisms (SNP) of ELOVL6 and T2DM pathogenesis, we conducted a case-control study of 610 Han Chinese individuals (328 newly diagnosed T2DM and 282 healthy subjects). Insulin resistance and islet first-phase secretion function were evaluated by assessment of insulin resistance in a homeostasis model (HOMA-IR) and an arginine stimulation test. Three SNPs of the ELOVL6 gene were genotyped with polymerase chain reaction-restriction fragment length polymorphism, with DNA sequencing used to confirm the results. Only genotypes TT and CT of the ELOVL6 SNP rs12504538 were detected in the samples. Genotype CC was not observed. The T2DM group had a higher frequency of the C allele and the CT genotype than the control group. Subjects with the CT genotype had higher HOMA-IR values than those with the TT genotype. In addition, no statistical significance was observed between the genotype and allele frequencies of the control and T2DM groups for SNPs rs17041272 and rs6824447. The study indicated that the ELOVL6 gene polymorphism rs12504538 is associated with an increased risk of T2DM, because it causes an increase in insulin resistance.