Diabetes mellitus (DM) is a global health concern characterized by a deficiency in insulin production. Considering the systemic toxicity and limited efficacy associated with current antidiabetic medications, there is the utmost need for natural, plant-based alternatives. Herbal medicines have experienced exponential growth in popularity globally in recent years for their natural origins and minimal side effects. Ecuador has a rich cultural history in ethnobotany that plays a crucial role in its people's lives. This study identifies 27 Ecuadorian medicinal plants that are traditionally used for diabetes treatment and are prepared through infusion, decoction, or juice, or are ingested in their raw forms. Among them, 22 plants have demonstrated hypoglycemic or anti-hyperglycemic properties that are rich with bioactive phytochemicals, which was confirmed in several in vitro and in vivo studies. However, Bryophyllum gastonis-bonnieri, Costus villosissimus, Juglans neotropica, Pithecellobium excelsum, and Myroxylon peruiferum, which were extensively used in traditional medicine preparation in Ecuador for many decades to treat diabetes, are lacking in pharmacological elucidation. The Ecuadorian medicinal plants used to treat diabetes have been found to have several bioactive compounds such as flavonoids, phenolics, fatty acids, aldehydes, and terpenoids that are mainly responsible for reducing blood sugar levels and oxidative stress, regulating intestinal function, improving insulin resistance, inhibiting α-amylase and α-glucosidase, lowering gluconeogenic enzymes, stimulating glucose uptake mechanisms, and playing an important role in glucose and lipid metabolism. However, there is a substantial lack of integrated approaches between the existing ethnomedicinal practices and pharmacological research. Therefore, this review aims to discuss and explore the traditional medicinal plants used in Ecuador for treating DM and their bioactive phytochemicals, which are mainly responsible for their antidiabetic properties. We believe that the use of Ecuadorian herbal medicine in a scientifically sound way can substantially benefit the local economy and industries seeking natural products.

• Klíčová slova
• antidiabetic, antihyperglycemic, bio-active compound, hypoglycemic, medicinal plant,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Metabolism of fibronectin, the protein that plays a key role in the healing of wounds, is changed in the patients with diabetes mellitus. Fibronectin can interact with other proteins and proteoglycans and organise them to form the extracellular matrix, the basis of the granulation tissue in healing wounds. However, diabetic foot ulcers (DFUs) suffer from inadequate deposition of this protein. Degradation prevails over fibronectin synthesis in the proteolytic inflammatory environment in the ulcers. Because of the lack of fibronectin in the wound bed, the assembly of the extracellular matrix and the deposition of the granulation tissue cannot be started. A number of methods have been designed that prevents fibronectin degradation, replace lacking fibronectin or support its formation in non-healing wounds in animal models of diabetes. The aim of this article is to review the metabolism of fibronectin in DFUs and to emphasise that it would be useful to pay more attention to fibronectin matrix assembly in the ulcers when laboratory methods are translated to clinical practice.

• Klíčová slova
• diabetes, extracellular matrix, fibronectin, ulcer, wound healing,
• MeSH
• diabetes mellitus * metabolismus   MeSH
• diabetická noha * terapie   MeSH
• extracelulární matrix MeSH
• fibronektiny MeSH
• hojení ran MeSH
• hyperglykemie * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• fibronektiny MeSH

Diabetes mellitus is characterized by long standing hyperglycemia leading to numerous life-threatening complications. For type 1 diabetes mellitus, resulting from selective destruction of insulin producing cells by exaggerated immune reaction, the only effective therapy remains exogenous insulin administration. Despite accurate compliance to treatment of certain patients, transient episodes of hyperglycemia cannot be completely eliminated by this symptomatic treatment. Novel immunotherapeutic approaches based on tolerogenic dendritic cells, T regulatory cells and mesenchymal stem cells (MSCs) have been tested in clinical trials, endeavoring to directly modulate the autoimmune destruction process in pancreas. However, hyperglycemia itself affects the immune system and the final efficacy of cell-based immunotherapies could be affected by the different glycemic control of enrolled patients. The present review explores the impact of hyperglycemia on immune cells while providing greater insight into the molecular mechanisms of high glucose action and subsequent metabolic reprogramming of different immune cells. Furthermore, over-production of mitochondrial reactive oxygen species, formation of advanced glycation end products as a consequence of hyperglycemia and their downstream signalization in immune cells are also discussed. Since hyperglycemia in patients with type 1 diabetes mellitus might have an impact on immune-interventional treatment, the maintenance of a tight glucose control seems to be beneficial in patients considered for cell-based therapy.

• Klíčová slova
• cell-based therapy, dendritic cells, diabetes mellitus, hyperglycemia, immune tolerance,
• MeSH
• dendritické buňky imunologie   metabolismus   transplantace   MeSH
• diabetes mellitus 1. typu imunologie   MeSH
• hyperglykemie imunologie   MeSH
• imunologická tolerance účinky léků   MeSH
• imunoterapie adoptivní metody   MeSH
• klinické zkoušky jako téma MeSH
• lidé MeSH
• mezenchymální kmenové buňky imunologie   MeSH
• mitochondrie metabolismus   MeSH
• monitorování fyziologických funkcí MeSH
• přeprogramování buněk MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• regulační T-lymfocyty imunologie   transplantace   MeSH
• transplantace mezenchymálních kmenových buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• reaktivní formy kyslíku MeSH

Microvascular complications in diabetes are associated with poor long-term diabetes control as measured by HbA1c levels. Glucose fluctuations are related to oxidative stress, endothelial dysfunction, and inflammation, factors traditionally associated with the pathogenesis of vascular damage. Glucose variability has been associated with macrovascular disease in some studies but any association with microvascular disease remains controversial. This overview summarizes recent findings in the field of glucose variability and its possible relationship with retinopathy, nephropathy and neuropathy. It is concluded that randomized prospective follow-up trials could possibly help estimate whether short-term glucose variability should be considered as an independent risk factor for microvascular complications in diabetes.

• Klíčová slova
• Glucose variability, HbA1c variability, Microvascular complications, Type 1 and Type 2 diabetes,
• MeSH
• diabetické angiopatie metabolismus   MeSH
• glykovaný hemoglobin metabolismus   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• mikrocévy patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• krevní glukóza MeSH

BACKGROUND: Diabetic cardiomyopathy is associated with a number of functional and structural pathological changes such as left ventricular dysfunction, cardiac remodeling, and apoptosis. The primary cause of diabetic cardiomyopathy is hyperglycemia, the metabolic hallmark of diabetes. Recent studies have shown that a diabetic environment suppresses hypoxia-inducible factor (HIF)-1α protein stability and function. The aim of this study was to analyze the functional role of HIF-1α in the development of diabetic cardiomyopathy. We have hypothesized that the partial deficiency of HIF-1α may compromise cardiac responses under diabetic conditions and increase susceptibility to diabetic cardiomyopathy. METHODS: Diabetes was induced by streptozotocin in wild type (Wt) and heterozygous Hif1a knock-out (Hif1a+/-) mice. Echocardiographic evaluations of left ventricular functional parameters, expression analyses by qPCR and Western blot, and cardiac histopathology assessments were performed in age-matched groups, diabetic, and non-diabetic Wt and Hif1a+/- mice. RESULTS: Five weeks after diabetes was established, a significant decrease in left ventricle fractional shortening was detected in diabetic Hif1a+/- but not in diabetic Wt mice. The combination effects of the partial deficiency of Hif1a and diabetes affected the gene expression profile of the heart, including reduced vascular endothelial growth factor A (Vegfa) expression. Adverse cardiac remodeling in the diabetic Hif1a+/- heart was shown by molecular changes in the expression of structural molecules and components of the extracellular matrix. CONCLUSIONS: We have shown a correlation between heterozygosity for Hif1α and adverse functional, molecular, and cellular changes associated with diabetic cardiomyopathy. Our results provide evidence that HIF-1α regulates early cardiac responses to diabetes, and that HIF-1α deregulation may influence the increased risk for diabetic cardiomyopathy.

• Publikační typ
• časopisecké články MeSH

The aim of this study was to compare skin autofluorescence caused by advanced glycation end-products (AGEs) with biochemical markers of endothelial dysfunction and soluble receptor for AGEs (sRAGE) in patients with diabetes. Skin autofluorescence (AF) assessed by AGE-Reader was evaluated with sRAGE and other biochemical parameters in 88 patients with diabetes (47 Type 1/T1DM/ and 41 Type 2/T2DM/) and 20 controls. Skin AF was significantly higher in T1DM and T2DM in comparison to controls (2.39 ± 0.54, 2.63 ± 0.73 versus 1.96 ± 0.33 AU; P < 0.0001). Positive correlation of AF with sRAGE was detected in T1DM and T2DM (r = 0.37, P < 0.02 and r = 0.60, P < 0.0001), but not in controls. Significantly higher AF values were found in patients with positive albuminuria as compared to those with normal albuminuria. Similarly, higher AF was detected in patients with endothelial dysfunction expressed by vWF, ICAM-1, and VCAM-1. Multiple regression analysis revealed independent association of skin AF with age, sRAGE, and albumin-creatinine ratio in patients with diabetes (R (2) = 0.38). Our study confirms that AF is elevated in patients with diabetes, especially with positive albuminuria and endothelial dysfunction. The strong and independent relationship between AF and sRAGE supports the idea that AF may reflect AGEs/RAGE interactions. The exact mechanism remains to be established.

• Publikační typ
• časopisecké články MeSH

AIMS: The aim of this study was to evaluate the effect of acute glycemia increase on microvasculature and endothelium in Type 1 diabetes during hyperinsulinemic clamp. PATIENTS AND METHODS: Sixteen patients (51 ± 7 yrs) without complications were examined during iso- and hyperglycemic clamp (glucose increase 5.5 mmol·L(-1)). Insulin, lipid parameters, cell adhesion molecules and fibrinogen were analyzed. Microvascular reactivity (MVR) was measured by laser Doppler flowmetry. RESULTS: Maximum perfusion and the velocity of perfusion increase during PORH were higher in hyperglycemia compared to baseline (47 ± 16 versus 40 ± 16 PU, P < 0.01, and 10.4 ± 16.5 versus 2.6 ± 1.5 PU·s(-1), P < 0.05, resp.). Time to the maximum perfusion during TH was shorter and velocity of perfusion increase during TH higher at hyperglycemia compared to isoglycemic phase (69 ± 15 versus 77 ± 16 s, P < 0.05, and 1.4 ± 0.8 versus 1.2 ± 0.7 PU·s(-1), P < 0.05, resp.). An inverse relationship was found between insulinemia and the time to maximum perfusion during PORH (r = -0.70, P = 0.007). CONCLUSION: Acute glycemia did not impair microvascular reactivity in this clamp study in Type 1 diabetic patients. Our results suggest that insulin may play a significant role in the regulation of microvascular perfusion in patients with Type 1 diabetes through its vasodilation effect and can counteract the effect of acute glucose fluctuations.

• MeSH
• cévní endotel cytologie   MeSH
• diabetes mellitus 1. typu patofyziologie   terapie   MeSH
• dospělí MeSH
• glykemický clamp * MeSH
• hyperglykemie patofyziologie   terapie   MeSH
• inzulin metabolismus   MeSH
• kalibrace MeSH
• komplikace diabetu patologie   MeSH
• krevní glukóza metabolismus   MeSH
• laser doppler flowmetrie metody   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikrocirkulace MeSH
• oxidační stres MeSH
• perfuze MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inzulin MeSH
• krevní glukóza MeSH