Deuterohemin-AlaHisLys mitigates the symptoms of rats with non-insulin dependent diabetes mellitus by scavenging reactive oxygen species and activating the PI3-K/AKT signal transduction pathway

Lei, Liyan; Zhang, Guangji; Li, Pengfei; Zhang, Yuan; Guo, Yutong; Zhang, Wenqi; Zhang, Wenbo; Hu, Bing; Wang, Liping

doi:10.1016/j.cbi.2014.05.008

Cited by 8 publications

(4 citation statements)

References 40 publications

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“…DhHP-6 is a MP-11 mimetic with a porphyrin ring at its N-terminus. DhHP-3, a homolog of DhHP-6, mitigated the symptom of rats with T2DM by intraperitoneal injection [18]. In our previous studies, we found that linear peptides covalently attached to the porphyrin ring became more stable in plasma.…”

Section: Discussionmentioning

confidence: 99%

“…Male C57BL/6J mice (weight, 20 ± 2 g) were induced to produce the T2DM model through high-fat fed (HFD)/STZ feeding as previously described [55]. After adjustable feeding for a week, mice were divided into the normal diet group and HFD (20% protein, 48% carbohydrate, and 22% fat, 20.08 kJ/g) group for four weeks [18]. Fasting blood glucose (FBG) levels of the HFD group receiving injection of STZ (100 mg/kg body weight) ≥11.2 mmol/L were considered diabetic after one week of treatment.…”

Section: Methodsmentioning

confidence: 99%

“…DhHP-6 also ameliorates Alzheimer’s disease-related pathology and cognitive decline in APPswe/PSEN1dE9 transgenic mouse models [17]. When injected, DhHP-3 (deuterohemin-Ala-His-Lys) improves the symptoms of T2DM rats [18].…”

Section: Introductionmentioning

confidence: 99%

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Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

Wang

Liang

et al. 2019

IJMS

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Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

Wang

Liang

et al. 2019

IJMS

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“…Based on previous articles about the T2DM model [ 10 – 12 ] and our preliminary experiment, a T2DM model was induced by high-fat diet and streptozotocin (STZ) injections. Rats were fed with a high-fat diet (22% fat, 48% carbohydrates, and 20% protein, 20.08 kJ/g) [ 13 , 14 ] for 4 weeks prior to intraperitoneal injection of a single 25 mg/kg dose of STZ (dissolved in 0.05 M citrate buffer at pH 4.5, prepared immediately before use). Two weeks after the STZ injection, rats were assessed by fasting blood glucose with blood collected from the tail vein.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

Wang

Han

2016

Journal of Diabetes Research

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In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic rats (P < 0.05). Furthermore, we also observed that TMXKP could significantly decrease IRS-1, IRS-2, PI3-K p85α, and AKT2 gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levels (P < 0.05) in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

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Extending Lifespan of Alzheimer’s Mode Nematode CL4176 Using a Novel Bifunctional Peptide with Inhibition of β-Amyloid Aggregation and Anti-oxidation

Zhang

et al. 2019

Chem. Res. Chin. Univ.

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Deuterohemin-AlaHisLys mitigates the symptoms of rats with non-insulin dependent diabetes mellitus by scavenging reactive oxygen species and activating the PI3-K/AKT signal transduction pathway

Cited by 8 publications

References 40 publications

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

Extending Lifespan of Alzheimer’s Mode Nematode CL4176 Using a Novel Bifunctional Peptide with Inhibition of β-Amyloid Aggregation and Anti-oxidation

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