Journal of Diabetes Research
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Nuclear Factor of Activated T Cells Is Activated in the Endothelium of Retinal Microvessels in Diabetic Mice The pathogenesis of diabetic retinopathy (DR) remains unclear but hyperglycemia is an established risk factor. Endothelial dysfunction and changes in Ca2+ signaling have been shown to precede the onset of DR. We recently demonstrated that high extracellular glucose activates the Ca2+ /calcineurin-dependent transcription factor NFAT in cerebral arteries and aorta, promoting the expression of inflammatory markers. Here we show, using confocal immunofluorescence, that NFAT is expressed in the endothelium of retinal microvessels and is readily activated by high glucose. This was inhibited by the NFAT blocker A-285222 as well as by the ectonucleotidase apyrase, suggesting a mechanism involving the release of extracellular nucleotides. Acute hyperglycemia induced by an IP-GTT (intraperitoneal glucose tolerance test) resulted in increased NFATc3 nuclear accumulation and NFAT-dependent transcriptional activity in retinal vessels of NFAT-luciferase reporter mice. In both Akita (Ins2+/− ) and streptozotocin- (STZ-) induced diabetic mice, NFAT transcriptional activity was elevated in retinal vessels.In vivo inhibition of NFAT with A-285222 decreased the expression ofOPN andICAM-1 mRNA in retinal vessels, prevented a diabetes driven downregulation of anti-inflammatory IL-10 in retina, and abrogated the increased vascular permeability observed in diabetic mice. Results identify NFAT signaling as a putative target for treatment of microvascular complications in diabetes.
Journal of Diabetes Research - Tập 2015 - Trang 1-14 - 2015
Polymorphisms of GLP-1 Receptor Gene and Response to GLP-1 Analogue in Patients with Poorly Controlled Type 2 Diabetes Aim . The relationship between genetic polymorphisms of the glucagon-like peptide-1 (GLP-1) receptor (GLP1R ) gene and unresponsiveness to GLP-1 analogue treatment in patients with poorly controlled type 2 diabetes mellitus (DM) is unclear.Methods . Thirty-six patients with poorly controlled type 2 DM were enrolled and they received six days of continuous subcutaneous insulin infusion for this study. After the normalization of blood glucose in the first 3 days, the patients then received a combination therapy with injections of the GLP-1 analogue, exenatide, for another 3 days. All 13 exons and intron-exon boundaries of theGLP1R gene were amplified to investigate the association.Results . The short tandem repeat at 8GA/7GA (rs5875654) had complete linkage disequilibrium (LD, withr 2 = 1 GLP1R gene variation with clinical response of GLP1 analogue showed the missense rs3765467 and rs761386 significantly associated with changes in the standard deviation of plasma glucose (SDP G baseline - SDP G treatment with GLP-1 analogue P = 0 . 041 P Conclusion . The variable response to the GLP-1 analogue was not statistically correlated with polymorphisms of theGLP1R gene in patients with poorly controlled type 2 DM.
Journal of Diabetes Research - Tập 2015 - Trang 1-10 - 2015
The Insulin‐Like Growth Factor System The insulin‐like growth factor (IGF) system in ubiquitous
and plays a role in every tissue of the body. It is comprised
of ligands, receptors and binding proteins, each with
specific functions. While it plays an essential role in embryonic
and post‐natal development, the IGF system is also
important in normal adult physiology. There are now numerous
examples of diseases such as diabetes, cancer, and
malnutrition in which the IGF system is a major player and,
not surprisingly, there are attempts to affect these disorders
by manipulating the system.
Journal of Diabetes Research - Tập 4 Số 4 - Trang 205-212 - 2003
Blocking AGE-RAGE Signaling Improved Functional Disorders of Macrophages in Diabetic Wound Advanced glycosylation end products (AGEs) accumulate in diabetic wounds. Interactions between AGEs and their receptor (RAGE) leads to dermatologic problems in diabetes. Macrophage, which plays important roles in wound healing, highly expresses RAGE. Therefore, we investigated whether RAGE-expressing macrophages might be responsible for impaired wound healing on diabetes. We used anti-RAGE antibody applied topically on diabetic wounds. After confirming that wound healing was improved in anti-RAGE antibody group compared with normal mice, our results showed that macrophages appeared insufficient in the early stage and fading away slowly in the later proliferative phase compared with the control group, which was ameliorated in anti-RAGE antibody-applied wounds. Blocking AGE-RAGE signaling also increased neutrophils phagocytized by macrophages and promoted the phenotypic switch of macrophages from proinflammatory to prohealing activities. In vitro, phagocytosis of THP-1 (M0) and lipopolysaccharide- (LPS-) induced (M1) macrophages was impaired by treatment with AGEs, while IL-4- and IL-13-induced (M2) macrophages was not. Finally, AGEs increased the proinflammatory response of M1 macrophages, while inhibiting the polarization and anti-inflammatory functions of M2 macrophages. In conclusion, inhibition of AGE-RAGE signaling improved functional disorders of macrophages in the early inflammatory phase, which promoted the healing of wounds in diabetic mice.
Journal of Diabetes Research - Tập 2017 - Trang 1-10 - 2017
Metformin Improves Overall Survival of Colorectal Cancer Patients with Diabetes: A Meta-Analysis Introduction . Diabetic population has a higher risk of colorectal cancer (CRC) incidence and mortality than nondiabetics. The role of metformin in CRC prognosis is still controversial. The meta-analysis aims to investigate whether metformin improves the survival of diabetic CRC patients.Methods . PubMed, EMBASE, and Cochrane Library were searched till July 1, 2016. Cohort studies were included. All articles were evaluated by Newcastle-Ottawa Scale. Hazard Ratios (HRs) with 95% confidence intervals (CIs) for each study were calculated and pooled HRs with corresponding 95% CIs were generated using the random-effects model. Heterogeneity and publication bias were assessed.Results . We included seven cohort studies with a medium heterogeneity (I 2 p = 0.03 3 Conclusions . Metformin prolongs the OS of diabetic CRC patients, but it does not affect the CRC-specific survival. Metformin may be a good choice in treating CRC patients with diabetes mellitus in clinical settings.
Journal of Diabetes Research - Tập 2017 - Trang 1-8 - 2017
Comparative Study of the Antioxidant Effects of Metformin, Glibenclamide, and Repaglinide in Alloxan-Induced Diabetic Rats Diabetes mellitus is one of the serious global health problems affecting a significant proportion of both developed and developing countries. Overproduction of free radicals and oxidative stress has been associated with the development of diabetic complications. In the present study, the antioxidant effects of metformin (MET), glibenclamide (GLI), and repaglinide (REP) were evaluated in alloxan-induced diabetic rats. The findings from this study may possibly help in understanding the efficacy of these standard drugs in managing the complications arising from diabetes mellitus (DM). Alloxan (130 mg/kg BW) was administered as a single dose to induce diabetes. Four (4) groups of rats (n = 6 p < 0.05
Journal of Diabetes Research - Tập 2016 - Trang 1-5 - 2016
Ursodeoxycholic Acid Attenuates Endoplasmic Reticulum Stress-Related Retinal Pericyte Loss in Streptozotocin-Induced Diabetic Mice Loss of pericytes, an early hallmark of diabetic retinopathy (DR), results in breakdown of the blood-retinal barrier. Endoplasmic reticulum (ER) stress may be involved in this process. The purpose of this study was to examine the effects of ursodeoxycholic acid (UDCA), a known ameliorator of ER stress, on pericyte loss in DR of streptozotocin- (STZ-) induced diabetic mice. To assess the extent of DR, the integrity of retinal vessels and density of retinal capillaries in STZ-induced diabetic mice were evaluated. Additionally, induction of ER stress and the unfolded protein response (UPR) were assessed in diabetic mice and human retinal pericytes exposed to advanced glycation end products (AGE) or modified low-density lipoprotein (mLDL). Fluorescein dye leakage during angiography and retinal capillary density were improved in UDCA-treated diabetic mice, compared to the nontreated diabetic group. Among the UPR markers, those involved in the protein kinase-like ER kinase (PERK) pathway were increased, while UDCA attenuated UPR in STZ-induced diabetic mice as well as AGE- or mLDL-exposed retinal pericytes in culture. Consequently, vascular integrity was improved and pericyte loss reduced in the retina of STZ-induced diabetic mice. Our findings suggest that UDCA might be effective in protecting against DR.
Journal of Diabetes Research - Tập 2017 - Trang 1-10 - 2017
Oxidative Stress and Diabetic Retinopathy Oxygen metabolism is essential for sustaining aerobic life, and normal cellular homeostasis works on a fine balance between the formation and elimination of reactive oxygen species (ROS). Oxidative stress, a cytopathic consequence of excessive production of ROS and the suppression of ROS removal by antioxidant defense system, is implicated in the development of many diseases, including Alzheimer′s disease, and diabetes and its complications. Retinopathy, a debilitating microvascular complication of diabetes, is the leading cause of acquired blindness in developed countries. Many diabetes‐induced metabolic abnormalities are implicated in its development, and appear to be influenced by elevated oxidative stress; however the exact mechanism of its development remains elusive. Increased superoxide concentration is considered as a causal link between elevated glucose and the other metabolic abnormalities important in the pathogenesis of diabetic complications. Animal studies have shown that antioxidants have beneficial effects on the development of retinopathy, but the results from very limited clinical trials are somewhat ambiguous. Although antioxidants are being used for other chronic diseases, controlled clinical trials are warranted to investigate potential beneficial effects of antioxidants in the development of retinopathy in diabetic patients.
Journal of Diabetes Research - Tập 2007 Số 1 - 2007
Classification and Differential Diagnosis of Diabetic Nephropathy Diabetic nephropathy (DN) is a major cause of end-stage renal disease throughout the world in both developed and developing countries. This review briefly introduces the characteristic pathological changes of DN and Tervaert pathological classification, which divides DN into four classifications according to glomerular lesions, along with a separate scoring system for tubular, interstitial, and vascular lesions. Given the heterogeneity of the renal lesions and the complex mechanism underlying diabetic nephropathy, Tervaert classification has both significance and controversies in the guidance of diagnosis and prognosis. Applications and evaluations using Tervaert classification and indications for renal biopsy are summarized in this review according to recent studies. Meanwhile, differential diagnosis with another nodular glomerulopathy and the situation that a typical DN superimposed with a nondiabetic renal disease (NDRD) are discussed and concluded in this review.
Journal of Diabetes Research - Tập 2017 - Trang 1-7 - 2017
Prevalence of Gestational Diabetes Mellitus in Eastern and Southeastern Asia: A Systematic Review and Meta-Analysis Aim . To review the prevalence of gestational diabetes mellitus (GDM) in Eastern and Southeastern Asia.Methods . We systematically searched for observational studies on GDM prevalence from January 2000 to December 2016. Inclusion criteria were original English papers, with full texts published in peer-reviewed journals. The quality of included studies was evaluated using the guidelines of the National Health and Medical Research Council, Australia. Fixed effects and random effects models were used to estimate the summary prevalence of GDM and the corresponding 95% confidence intervals (CI).Results. A total of 4415 papers were screened, and 48 studies with 63 GDM prevalence observations were included in the final review. The pooled prevalence of GDM was 10.1% (95% CI: 6.5%–15.7%), despite substantial variations across nations. The prevalence of GDM in lower- or upper-middle income countries was about 64% higher than in their high-income counterparts. Moreover, the one-step screening method was twice more likely to be used in diagnosing GDM when compared to the two-step screening procedure.Conclusions. The prevalence of GDM in Eastern and Southeastern Asia was high and varied among and within countries. There is a need for international uniformity in screening strategies and diagnostic criteria for GDM.
Journal of Diabetes Research - Tập 2018 - Trang 1-10 - 2018
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