To analyze the relationship between cutaneous glycometabolic disorders and cutaneous neuropathy in diabetic rats, and to look for the mechanism of neuropathy and impaired wound healing.
Eighty male ...SD rats were randomly divided into the normal control group (NC, n = 20), diabetic group (D, n = 20), aminoguanidine-interfered group (AI, n = 20), and insulin-interfered group (II, n = 20) by drawing lots. Diabetes was reproduced in rats of D, AI, and II groups with intraperitoneal injection of streptozotocin (STZ). Then, rats in AI group were fed with 100 mg×kg(-1)×d(-1) aminoguanidine, while rats in II group were subcutaneously injected with insulin for satisfactory control of blood glucose. Changes in mechanical and heat pain thresholds of pad of hind limb were measured at post injection week (PIW) 2, 4, 8. Skin specimens were collected during PIW 2-8 from pads for determination of contents of glucose, advanced glycation end product (AGE), substance P (SP), calcitonin gene-related peptide (CGRP), and observatio
To investigate the effects of aminoguanidine cream on the proliferation of keratinocytes (KC), content of advanced glycosylation end products (AGE) and oxidative stress in skin tissue of rats with ...diabetes.
Stearic acid, liquid paraffin, vaseline, lanolin, isopropyl myristate fat, glycerol, 50 g/L alcohol paraben, aminoguanidine hydrochloride etc. were mixed in certain proportion to make aminoguanidine cream, and cream without aminoguanidine was used as matrix. The dorsal skin of normal rats were harvested and treated by aminoguanidine cream with dose of 5, 10 g/L, or 5 g/L together with 10 g/L azone. The transdermal effect was respectively measured at post treatment hour 2, 4, 7, 10, 12, 24. Thirty SD rats were divided into normal control (NC, n = 6), diabetes (D, n = 8), aminoguanidine cream-interfered (AI, n = 8), matrix cream-interfered groups (MI, n = 8) according to the random number table. Diabetes was reproduced by intraperitoneal injection of STZ (65 mg/kg) in rats of D, AI, and MI groups, and rats i
Advanced glycation end products (AGEs) formation is implicated in diabetic complications. Exogenous AGEs, namely glycotoxins, are present in certain foods and are absorbed from the gastrointestinal ...tract. Experimental data suggest that lifestyle interventions reducing their content in diet have beneficial effect.
Fourteen healthy (age: 42.14 +/- 12.38 years; body mass index BMI: 27.85 +/- 7.06 kg/m2) and ten women with type 2 diabetes (T2DM) (age: 48.70 +/- 9.31 years; BMI: 32.55 +/- 7.14 kg/m2) were enrolled in the study. A meal rich in AGEs was provided in a two-day protocol and on day 2, 240 mg of Orlistat were administered post-meal.
On day 1, serum AGEs levels showed a rise at 3 hours post-meal compared to baseline values in both groups (controls: 12.2%; P<0.001), T2DM: 2.6%; P=0.013), but at 5 hours post-meal only in the controls (control: 12.2%; P<0.001); T2DM: 1.9%; P=0.075). On day 2 at 3 hours post-meal control values showed a rise of 3.1% (P=0.003); T2DM of 1.9% (P=0.013); at 5 hours post-meal rise for controls was 4.6% (P=0.012); and for T2DM was 1.8% (P=0.009). The corresponding rise was significantly lower on day 2 only in controls at 3 and 5 hours post-meal (P=0.003; P=0.05, respectively).
Orlistat reduced the absorption of glycotoxins acutely and improved the metabolic profile in the control group, without an apparent beneficial effect in the diabetic group. The clinical significance of this observation should be further investigated in normal population, while in diabetics long-term studies may be required to demonstrate possible clinically significant effects.
To investigate the effects of advanced glycation end products (AGE) on the biological behavior of neutrophils in vitro, to look for the relationship between accumulation of AGE and abnormal ...inflammation in wound healing in diabetic mellitus patients.
Neutrophils were isolated from SD rats and incubated in vitro. The cells were divided into four groups according to different concentrations of AGE in cell suspension: control group (C, with treatment of RPMI - 1640), A group (with treatment of 0.315 mg/mL AGE + RPMI - 1640), B group (with treatment of 0.625 mg/mL AGE + RPMI - 1640), D group (with treatment of 1.250 mg/mL AGE + RPMI - 1640). Activity of neutrophils were determined by MTT colorimetric assay. Selectin-L mRNA expressions were analyzed by reversible transcription polymerase chain reaction (RT -PCR) technique. The levels of reactive oxygen species (ROS) in neutrophils were measured with DCFH-DA method. The protein concentration of neutrophil elastase (NE) was assayed by ELISA.
The activity of neutroph
To investigate the effect of advanced glycosylation end products (AGE) on cell cycle of epidermal keratinocyte and its possible signal pathway.
150 mg/L AGE-human serum albumin (AGE-HSA) was prepared ...in vitro. Primary cultured keratinocytes in logarithmic growth phase were harvested and divided randomly into: A group with treatment of defined keratinocyte-SFM (DK-SFM) serum-free medium, B group (with treatment of DK-SFM medium including 150 mg/L AGE-HSA), C group (with DK-SFM medium after treatment of U0126) and group D (with D K-SFM medium including 150 mg/L AGE-HSA after treatment of U0126). Cell cycle distributions were analyzed by flow cytometer. The protein levels of cyclin D1, cyclin B1, CDK4 and p44/42 MAPK were measured by Western blot.
Compared with those of A group, the percentage of S-phase and G2/M-phase keratinocytes were decreased obviously in B group, the percentages of G2/M -phase keratinocytes showed the same tendency in C and D groups (9.7 +/- 1.1)% , (9.8 +/- 0.7)%, respectively, P <0.05