Microvascular metabolism in diabetes

Kern, Timothy S.; Engerman, Ronald L.

doi:10.1016/0026-0495(86)90183-6

Cited by 14 publications

(5 citation statements)

References 53 publications

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“…Furthermore, our study suggested that the abundance of HEXITOLDEGSUPER-PWY pathway (superpathway of hexitol degradation) in vaginal microbiota was associated with sPTB. Bacteria can utilize hexitols as a source of carbon and energy; hence, a high abundance superpathway of hexitol degradation reflects a high load of bacteria [ 63 ]. A recent study showed that the high load bacteria in vagina might trigger the sPTB.…”

Section: Discussionmentioning

confidence: 99%

“…Hexitol production and accumulation has been implicated in the pathogenesis of diabetic complications [ 67 ]. Hexitol production can lead to the basement membrane thickening in microvessels, which is demonstrated in diabetic microvascular disease [ 63 , 67 , 68 ]. The basement membrane thickening in fetal membranes will lead to an increase in membrane fragility and premature rupture of membranes.…”

Section: Discussionmentioning

confidence: 99%

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Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women

Kan

et al. 2022

BioMed Research International

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Objective. The effect of vaginal microbiota on spontaneous preterm birth (sPTB) has not been fully addressed, and few studies have explored the associations between vaginal taxa and sPTB in the gestational diabetes mellitus (GDM) and non-GDM groups, respectively. Study Design. To minimize external interference, a total of 41 pregnant women with sPTB and 308 controls (pregnant women without sPTB) from same regain were enrolled in this case-cohort study. Controls were randomly selected at baseline. With the exception of GDM, other characteristics were not significantly different between the two groups. Vaginal swabs were collected at early second trimester. Using 16S amplicon sequencing, the main bioinformatics analysis was performed on the platform of QIIME 2. Vaginal microbiota traits of the sPTB group were compared with controls. Finally, the effects of binary taxa on sPTB in the GDM group and the non-GDM group were analyzed, respectively. Results. The proportion of GDM in the sPTB (19.51%) was higher than the controls (7.47%, P = 0.018 ). The vaginal microbiota of pregnant women with sPTB exhibited higher alpha diversity metrics (observed features, P = 0.001 ; Faith’s phylogenetic diversity, P = 0.013 ) and different beta diversity metrics (unweighted UniFrac, P = 0.006 ; Jaccard’s distance, P = 0.004 ), compared with controls. The presence of Lactobacillus paragasseri/gasseri (aOR: 3.12, 95% CI: 1.24-7.84), Streptococcus (aOR: 3.58, 95% CI: 1.68-7.65), or Proteobacteria (aOR: 3.39, 95% CI: 1.55-7.39) was associated with an increased risk of sPTB in the non-GDM group ( P < 0.05 ). However, the relative abundance of novel L. mulieris (a new species of the L. delbrueckii group) was associated with a decreased risk of sPTB (false discovery rate, 0.10) in all pregnant women. Conclusion. GDM may modify the association of vaginal taxa with sPTB, suggesting that maternal GDM should be considered when using vaginal taxa to identify pregnant women at high risk of sPTB.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women

Kan

et al. 2022

BioMed Research International

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“…Nevertheless, the association among hyperglycemia, diabetes, and retinopathy remains to be mechanistically defined (Addison et al, 1970;Harik and LaManna, 1988;Kern and Engerman, 1996;Mann et al, 2003). The primary mechanisms implicated in the pathogenesis of diabetic retinopathy are thought to be biochemical and hemodynamic, all of which are dependent on excessive transport (GLUT-1) or accumulation of glucose (Kumagai, 1999;Lorenzi et al, 1986) within the retina or its microvasculature (Kador et al, 1988;Kern and Engerman, 1986;Mizutani et al, 1996). The results of this study reveal that the increased retinal glucose levels in the group of diabetic rats are not a consequence of increased glucose crossing the BRB.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

Puchowicz

Magness

et al. 2004

J Cereb Blood Flow Metab

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Summary:Diabetes is associated with extensive microvascular pathology and decreased expression of the glucose transporter (GLUT-1) in retina, but not brain. To explore the basis of these differences, the authors simultaneously measured glucose influx (mol · g −1 · min) and blood flow (mL · g −1 · min −1 ) in retina and brain cortex of nondiabetic control rats (normoglycemic and acute-hyperglycemic) and in rats with streptozotocin-induced diabetes (with or without aminoguanidine (AMG) treatment) using a single-pass, dual-label indicator method. In addition, tissue glucose and adenosine triphosphate (nmol/mg dry weight) levels were measured. Glucose influx in retina exceeded that of cortex by about threefold for both the nondiabetic and diabetic groups. In contrast, blood flow in retina was significantly lower than in cortex by about threefold for each group. Retinal and cortical glucose influx in the diabetic rats was lower than in the nondiabetic acute-hyperglycemic group, but not in the normoglycemic group. Blood flow in these tissues remained relatively unchanged with glycemic conditions. The glucose levels in the diabetic retina (aminoguanidine untreated and aminoguanidine treated) were fourfold to sixfold greater than the nondiabetic retina. The cortical glucose levels remained unchanged in all groups. These data suggest that the accumulation of glucose in the diabetic retina cannot be explained by increased endothelialglucose uptake or increased vascular membrane permeability.

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“…As for the role of mitochondria and ROS in DR, retinal endothelial cells isolated from type 2 diabetic patients have increased mitochondrial fission and ROS overproduction [20], and the retina from DR patients also shows downregulated mitochondrial fusion [21]. Historically, DR has been investigated and treated as a complication of the vasculature [22, 23]. However, increasing evidence shows that retinal neural dysfunction precedes any microvascular complication [24].…”

Section: Introductionmentioning

confidence: 99%

Melatonin Affects Mitochondrial Fission/Fusion Dynamics in the Diabetic Retina

Chang

Shi

et al. 2019

Journal of Diabetes Research

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Mitochondrial fission and fusion are dependent on cellular nutritional states, and maintaining this dynamics is critical for the health of cells. Starvation triggers mitochondrial fusion to maintain bioenergetic efficiency, but during nutrient overloads (as with hyperglycemic conditions), fragmenting mitochondria is a way to store nutrients to avoid waste of energy. In addition to ATP production, mitochondria play an important role in buffering intracellular calcium (Ca2+). We found that in cultured 661W cells, a photoreceptor-derived cell line, hyperglycemic conditions triggered an increase of the expression of dynamin-related protein 1 (DRP1), a protein marker of mitochondrial fission, and a decrease of mitofusin 2 (MFN2), a protein for mitochondrial fusion. Further, these hyperglycemic cells also had decreased mitochondrial Ca2+ but increased cytosolic Ca2+. Treating these hyperglycemic cells with melatonin, a multifaceted antioxidant, averted hyperglycemia-altered mitochondrial fission-and-fusion dynamics and mitochondrial Ca2+ levels. To mimic how people most commonly take melatonin supplements, we gave melatonin to streptozotocin- (STZ-) induced type 1 diabetic mice by daily oral gavage and determined the effects of melatonin on diabetic eyes. We found that melatonin was not able to reverse the STZ-induced systemic hyperglycemic condition, but it prevented STZ-induced damage to the neural retina and retinal microvasculature. The beneficial effects of melatonin in the neural retina in part were through alleviating STZ-caused changes in mitochondrial dynamics and Ca2+ buffering.

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Microvascular metabolism in diabetes

Cited by 14 publications

References 53 publications

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women

Differential Effect of Vaginal Microbiota on Spontaneous Preterm Birth among Chinese Pregnant Women

Comparison of Glucose Influx and Blood Flow in Retina and Brain of Diabetic Rats

Melatonin Affects Mitochondrial Fission/Fusion Dynamics in the Diabetic Retina

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