1.Exosomes and their roles in diabetes mellitus and its complications: from pathogenic, diagnostic and therapeutical perspectives.
Yin SHOU ; Yu-Hang MA ; Li HU ; Ping XU ; Wei-Bo ZHANG ; Yuan GAO ; Bi-Meng ZHANG
Acta Physiologica Sinica 2019;71(6):917-934
Exosome is a kind of nanoscale-size extracellular vesicles secreted by the means of cell active stimulation with outer membrane structure of vacuoles corpuscle. It can carry and transfer a lot of biological molecules, such as DNA fragments, circular RNA (circRNA), messenger RNA (mRNA), microRNA (miRNA), functional proteins, transcription factors, etc., so as to achieve the goal of information transmission between cells. The relationship between exosomes and diabetes has received extensive attention in recent years. The exosomes play an important role in insulin sensitivity, glucose homeostasis and vascular endothelial function. This paper reviews the role of exosomes in the occurrence and development of diabetes and its complications, and discusses the role and prospect of exosomes as a target for diabetes treatment and its role in the diagnosis and treatment of diabetes.
Diabetes Mellitus
;
diagnosis
;
physiopathology
;
therapy
;
Exosomes
;
metabolism
;
Humans
;
Insulin Resistance
;
physiology
;
MicroRNAs
;
metabolism
;
RNA, Messenger
;
metabolism
2.Cellular and Molecular Mechanisms Underlying Arterial Baroreceptor Remodeling in Cardiovascular Diseases and Diabetes.
Huiyin TU ; Dongze ZHANG ; Yu-Long LI
Neuroscience Bulletin 2019;35(1):98-112
Clinical trials and animal experimental studies have demonstrated an association of arterial baroreflex impairment with the prognosis and mortality of cardiovascular diseases and diabetes. As a primary part of the arterial baroreflex arc, the pressure sensitivity of arterial baroreceptors is blunted and involved in arterial baroreflex dysfunction in cardiovascular diseases and diabetes. Changes in the arterial vascular walls, mechanosensitive ion channels, and voltage-gated ion channels contribute to the attenuation of arterial baroreceptor sensitivity. Some endogenous substances (such as angiotensin II and superoxide anion) can modulate these morphological and functional alterations through intracellular signaling pathways in impaired arterial baroreceptors. Arterial baroreceptors can be considered as a potential therapeutic target to improve the prognosis of patients with cardiovascular diseases and diabetes.
Animals
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Baroreflex
;
physiology
;
Blood Pressure
;
physiology
;
Cardiovascular Diseases
;
metabolism
;
physiopathology
;
Diabetes Mellitus
;
metabolism
;
physiopathology
;
Humans
;
Ion Channels
;
metabolism
;
Pressoreceptors
;
metabolism
3.Neuromuscular Pharmacodynamics of Rocuronium in Diabetic Rats.
Xiao Wen LIU ; Rui Song GONG ; Zhen LIU ; Jun ZUO ; Jing ZHAO
Acta Academiae Medicinae Sinicae 2019;41(2):149-155
Objective To investigate diabetes-mediated changes in the neuromuscular pharmacodynamics of rocuronium in rats. Methods Diabetes mellitus was induced by a single injection of streptozotocin in rats.A total of 24 male SD rats were assigned to four groups using random number table:the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group(6 rats per group).The sciatic nerve was stimulated in a rain-of-four(TOF)pattern,and the twitch tension changes in the tibialis anterior muscle were demonstrated by mechanomyography after intravenous injection of rocuronium in vivo.The time course characteristics of rocuronium,including onset time,and the recovery time from rocuronium injection to TOF ratio 75%(RT75%)and 90%(RT90%),were recorded,and half maximal inhibitory concentration(IC)values of rocuronium were determined using a four-parameter dose response curve. Results Compared with the normal controls,the diabetic rats had significantly prolonged onset time of rocuronium,while the RT75% and RT90% were decreased at all rocuronium doses(P<0.001).The time course changes became increasingly significant as the duration of diabetes lengthened(P<0.001).The IC and 95% confidence interval values for rocuronium in the normal control group,diabetic 2-week group,diabetic 4-week group,and diabetic 8-week group were 0.37(0.35-0.38)mg/kg,0.44(0.43-0.46)mg/kg,0.59(0.57-0.61)mg/kg,and 0.64(0.61-0.66)mg/kg,respectively.IC values were significantly higher in the diabetic groups vs.normal control(P<0.001)and gradually increased as the duration of diabetes lengthened(P<0.001).Conclusion Diabetes is associated with the rat skeletal muscle hyposensitivity to rocuronium,which is featured by prolonged onset time of rocuronium,decreased RT 75% and RT 90%,and right shift of the cumulative dose-response curve of rocuronium.
Animals
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Diabetes Mellitus, Experimental
;
physiopathology
;
Male
;
Muscle, Skeletal
;
drug effects
;
Neuromuscular Nondepolarizing Agents
;
pharmacology
;
Random Allocation
;
Rats
;
Rats, Sprague-Dawley
;
Rocuronium
;
pharmacology
4.Epidemiological and pathophysiological evidence supporting links between obstructive sleep apnoea and Type 2 diabetes mellitus.
Chuen Peng LEE ; Clete A KUSHIDA ; John Arputhan ABISHEGANADEN
Singapore medical journal 2019;60(2):54-56
Obstructive sleep apnoea (OSA) and Type 2 diabetes mellitus (T2DM) are common diseases. The global prevalence of OSA is between 2% and 7% in general population cohorts. The worldwide prevalence of T2DM among adults (aged 20-79 years) was estimated to be 6.4%. The concurrent presence of OSA and T2DM can be expected in the same patient, given their high prevalence and similar predisposition. We reviewed the overlapping pathophysiology of OSA and T2DM in this article.
Adult
;
Aged
;
Continuous Positive Airway Pressure
;
Diabetes Mellitus, Type 2
;
complications
;
epidemiology
;
physiopathology
;
Female
;
Humans
;
Male
;
Middle Aged
;
Sleep Apnea, Obstructive
;
complications
;
epidemiology
;
physiopathology
;
therapy
;
Young Adult
5.Mechanisms of adiponectin protection against diabetes-induced vascular endothelial injury.
Acta Physiologica Sinica 2019;71(3):485-490
The incidence and mortality rates of diabetes with cardiovascular complications are continually rising, and diabetic cardiovascular disease is becoming a major public health issue that threatens human health. Acute endothelial dysfunction and chronic cellular damage caused by diabetes are important risk factors for diabetic cardiovascular disease and related mortality. Adiponectin is an adipocyte-derived molecule with significant cytoprotective effects, including the protection against diabetes-induced vascular endothelial injury. Here we review the mechanisms of adiponectin protective effects on acute vascular endothelial dysfunction and chronic structural damage induced by diabetes.
Adiponectin
;
physiology
;
Cardiovascular Diseases
;
complications
;
Diabetes Mellitus
;
pathology
;
Endothelium, Vascular
;
physiopathology
;
Humans
6.miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1.
Jie WU ; Xing-Hua QIN ; Zuo-Xu HOU ; Zi-Hao FU ; Guo-Hua LI ; Hong-Yan YANG ; Xing ZHANG ; Feng GAO
Acta Physiologica Sinica 2019;71(2):271-278
More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.
Animals
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Diabetes Mellitus, Experimental
;
physiopathology
;
Down-Regulation
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Insulin
;
Insulin Receptor Substrate Proteins
;
physiology
;
Insulin Resistance
;
MicroRNAs
;
genetics
;
Myocytes, Cardiac
;
physiology
;
Rats
7.Assessment of lower extremity muscle mass, muscle strength, and exercise therapy in elderly patients with diabetes mellitus.
Takuo NOMURA ; Toshihiro KAWAE ; Hiroaki KATAOKA ; Yukio IKEDA
Environmental Health and Preventive Medicine 2018;23(1):20-20
The increase in the proportion of elderly people in the population is one of the most remarkable sociodemographic phenomena of the twenty-first century. The number of patients with diabetes is also increasing worldwide with this demographic change. Given these facts, consideration of the problems the general elderly population is facing in the management of diabetes is essential. In this review article, we focus on sarcopenia, which is the decrease in lower extremity muscle mass and muscle strength accompanying aging, describe the relationship between sarcopenia and diabetes, and highlight the specific factors through which diabetes contributes to loss of muscle strength. The quantitative methods for evaluating lower extremity muscle strength will also be described. These methods hold the key to assessing the effectiveness of exercise therapy and optimizing the assessment of the degree of autonomy in the activities of daily living. Exercise is one of the basic treatments for type 2 diabetes and may also prevent and improve sarcopenia. This review discusses the aspects common to the two health conditions and elucidates the effectiveness and necessity of exercise as a preventive measure against diabetes among the elderly.
Aged
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Aged, 80 and over
;
Diabetes Mellitus, Type 2
;
physiopathology
;
prevention & control
;
Exercise Therapy
;
Female
;
Humans
;
Leg
;
physiopathology
;
Male
;
Muscle Strength
;
physiology
;
Muscle, Skeletal
;
physiology
;
Sarcopenia
;
physiopathology
;
prevention & control
8.Effect of type 2 diabetes mellitus on flavonoid pharmacokinetics and tissue distribution after oral administration of Radix Scutellaria extract in rats.
Xue-Ju ZHANG ; Shu LIU ; Jun-Peng XING ; Zhi-Qiang LIU ; Feng-Rui SONG
Chinese Journal of Natural Medicines (English Ed.) 2018;16(6):418-427
Radix Scutellaria is widely applied to the treatment of diabetes mellitus in China. Its main bioactive constituents contain baicalin, wogonoside, oroxyloside, and their aglycones. To investigate the effect of type 2 diabetes mellitus on both pharmacokinetics and tissue distribution of these flavonoid compounds, the six flavonoids in plasma and tissues from the normal and type 2 diabetic rats after oral administration of Radix Scutellaria extract were simultaneously measured by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method. The results showed that baicalin, wogonoside, and oroxyloside had higher C and AUC values (P < 0.05) in type 2 diabetic rats than that in normal rats and the tissue-distribution behaviors of the six flavonoid compounds in hearts, livers, spleens, lungs, kidneys, brains, pancreas, fat and muscle of the type 2 diabetic rats showed obviously differences from the normal rats (P < 0.05). In conclusion, the differences in the pharmacokinetics of oroxyloside and tissue distribution of the six flavanoids in Radix Scutellaria extract between diabetic and normal rats were found for the first time. The results from the present study provided a crucial basis for a better understanding of in vivo anti-diabetic mechanism of action of the six flavonoids from Radix Scutellaria.
Administration, Oral
;
Animals
;
Chromatography, High Pressure Liquid
;
Diabetes Mellitus, Experimental
;
drug therapy
;
metabolism
;
physiopathology
;
Drugs, Chinese Herbal
;
administration & dosage
;
chemistry
;
Flavonoids
;
analysis
;
chemistry
;
pharmacokinetics
;
Male
;
Molecular Structure
;
Plant Roots
;
chemistry
;
Rats
;
Rats, Wistar
;
Reproducibility of Results
;
Scutellaria baicalensis
;
chemistry
;
Tandem Mass Spectrometry
;
Tissue Distribution
;
physiology
9.Mori Cortex extract ameliorates nonalcoholic fatty liver disease (NAFLD) and insulin resistance in high-fat-diet/streptozotocin-induced type 2 diabetes in rats.
Li-Li MA ; Yan-Yan YUAN ; Ming ZHAO ; Xin-Rong ZHOU ; Tashina JEHANGIR ; Fu-Yan WANG ; Yang XI ; Shi-Zhong BU
Chinese Journal of Natural Medicines (English Ed.) 2018;16(6):411-417
Nonalcoholic fatty liver disease (NAFLD) and type 2 Diabetes Mellitus (T2DM) are highly prevalent diseases and are closely associated, with NAFLD being present in the majority of T2DM patients. In Asian traditional medicine, Mori Cortex is widely used for the treatment of diabetes and hyperlipidemia. However, whether it has a therapeutic effect on T2DM associated with NAFLD is still unknown. The present study showed that the oral treatment with Mori Cortex extract (MCE; 10 g·kg·d) lowered the blood lipid levels and reversed insulin resistance (IR) in high fat-diet/streptozotocin-induced type 2 diabetes in rats. The expression levels of sterol receptor element-binding protein-1c (SREBP-1c) and carbohydrate-responsive element binding protein (ChREBP), which are involved in steatosis in NAFLD rats, were measured in the liver samples. MCE decreased the protein and mRNA expression levels of SREBP-1c and ChREBP. In conclusion, down-regulation of SREBP-1c and ChREBP might contribute to the protective effect of MCE on hepatic injury and IR in the rats with T2DM associated with NAFLD.
Alanine Transaminase
;
blood
;
Animals
;
Aspartate Aminotransferases
;
blood
;
Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
;
genetics
;
Diabetes Mellitus, Type 2
;
blood
;
chemically induced
;
drug therapy
;
metabolism
;
Diet, High-Fat
;
adverse effects
;
Disease Models, Animal
;
Down-Regulation
;
drug effects
;
Insulin
;
blood
;
Insulin Resistance
;
physiology
;
Lipid Metabolism
;
drug effects
;
genetics
;
Liver
;
drug effects
;
physiopathology
;
Male
;
Morus
;
Non-alcoholic Fatty Liver Disease
;
blood
;
chemically induced
;
drug therapy
;
metabolism
;
Phytotherapy
;
Plant Extracts
;
pharmacology
;
therapeutic use
;
Rats
;
Rats, Sprague-Dawley
;
Streptozocin
10.Expression level of Dickkopf-1 protein in bone mesenchymal stem cells in Type 2 diabetic rats and its relationship with osteogenic activity.
Yan LI ; Zhitao LIU ; Zhaochen TONG ; Heqing HUANG ; Zhendong LIU
Journal of Central South University(Medical Sciences) 2018;43(9):971-981
To examine the growth activity and osteogenic differentiation of bone mesenchymal stem cells (BMSCs) in rats with Type 2 diabetes mellitus (T2DM) as well as the expression level of Dickkopf-1 (DKK-1) in bone marrow, and to explore the relationship between the osteogenic activity of BMSCs and the expression of DKK-1.
Methods: The BMSCs were isolated from T2DM rats and were cultured in vitro. The BMSCs were divided into a T2DM group and a control group. The proliferation of BMSCs was detected by cell counting kit-8 (CCK8). Apoptosis rate was detected by annexin V- fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining. In the osteogenic induction phase, the expression level of alkaline phosphatase (ALP) in BMSCs was detected by ALP staining and ALP activity assay kit. The osteogenic differentiation of BMSCs was analyzed by alizarin red staining and mineralized nodule quantification. In addition, the expression of Runx2 and DKK-1 in BMSCs was detected by qRT-PCR.
Results: Compared with the control group, the proliferation of BMSCs was decreased and the apoptosis was increased in the T2DM group (both P<0.01). In the osteogenic induction process of BMSCs, the expression of ALP significantly decreased, the formation of calcium nodules reduced, and the expression of osteoblast transcription factor Runx2 was down-regulated in the T2DM group compared with those in the control group (all P<0.01). The levels of DKK-1 protein and mRNA were up-regulated in the T2DM group, which were higher than those in the control group (both P<0.01). The levels of DKK-1 protein and mRNA were related to the increase of Runx2 (both P<0.01).
Conclusion: The growth activity of BMSCs and the potential of osteogenic differentiation are attenuated in the T2DM rats, which may be related to the increase of DKK-1 expression in BMSCs.
Animals
;
Bone Marrow Cells
;
Cell Differentiation
;
Cells, Cultured
;
Diabetes Mellitus, Experimental
;
Diabetes Mellitus, Type 2
;
physiopathology
;
Gene Expression Regulation
;
Intercellular Signaling Peptides and Proteins
;
genetics
;
Mesenchymal Stem Cells
;
Osteogenesis
;
genetics
;
Rats

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