Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
Humans ; Parkinson Disease/drug therapy* ; Diabetes Mellitus, Type 2/pathology* ; Signal Transduction/physiology* ; Receptor, Insulin/metabolism* ; Animals ; Insulin Resistance/physiology* ; Insulin/metabolism*

Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.
Humans ; Diabetic Nephropathies/drug therapy* ; Kidney/pathology* ; Anthraquinones/therapeutic use* ; Diabetes Mellitus

To explore the possible new mechanism of acupuncture in the treatment of diabetes mellitus type 2 (T2DM) based on the islet inflammatory response. Islet macrophages, pancreatic adipose cells and islet β cells all participate in the pathogenesis of T2DM, and the three could form a network interaction. Acupuncture could regulate the functional phenotype of islet macrophages, improve the ectopic deposition of pancreatic adipose and repair the function of islet β cells, and play a unique advantage of overall regulation. It is suggested that acupuncture can be a potential treatment strategy for T2DM.
Acupuncture Therapy ; Diabetes Mellitus, Type 2/therapy* ; Humans ; Insulin-Secreting Cells/pathology* ; Islets of Langerhans/pathology* ; Macrophages

Objective: To observe the effect of lipid regulating therapy on carotid atherosclerotic plaque in diabetic patients. Methods: The REACH study, conducted between March 2009 and February 2012, enrolled asymptomatic patients with magnetic resonance imaging (MRI) confirmed carotid atherosclerotic plaque, who had never taken lipid-lowering drugs. Patients were treated with a moderate dose of rosuvastatin for 24 months. Blood lipid levels were measured and carotid MRI was performed at baseline, 3 and 24 months after treatment. The volume of carotid wall and lipid-rich necrotic core (LRNC) were measured by image analysis software. This study retrospectively analyzed patients in the REACH study. Patients were divided into diabetes group and non-diabetic group. The changes of blood lipid level and MRI parameters of carotid atherosclerotic plaque were compared between the two groups and their correlation was analyzed. Results: A total of 38 patients with carotid atherosclerotic plaque were included in this study, including 13 patients (34.2%) in the diabetic group and 25 patients (65.8%) in the non-diabetic group. Baseline parameters were comparable between the two groups, except higher HbA1c level in diabetes group (P<0.05). Compared with baseline, the total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and triglyceride (TG) levels were significantly decreased at 3 and 24 months in both two groups (P<0.05). The change of high-density lipoprotein cholesterol (HDL-C) in diabetes group was not obvious, while it was significantly increased in non-diabetic group at 24 months ((1.38±0.33) mmol/l vs. (1.26±0.26) mmol/l, P<0.05). MRI results showed that the volume and percentage of LRNC remained unchanged at 3 months, slightly decreased at 24 months (64.86 (45.37, 134.56) mm³ vs. 75.76 (48.20, 115.64) mm³, P>0.05) and (15.84% (11.47%, 24.85%) vs. 16.95% (11.64%, 22.91%), P>0.05) in diabetic group. In non-diabetic group, the volume and percentage of LRNC were significantly decreased at 3 months (63.01 (44.25, 188.64) mm³ vs. 72.49 (51.91, 199.59) mm³, P<0.05) and (13.76% (8.81%, 27.64%) vs. 16.04% (11.18%, 27.05%), P<0.05) respectively. Both parameters further decreased to (55.63 (27.18, 179.40) mm³) and (12.71% (8.39%, 24.41%)) at 24 months (both P<0.05). Wall volume, lumen volume and percent wall volume (PWV) were not affected post therapy in both two groups(P>0.05). There were no correlations between the changes of plaque parameters including volume and percentage of LRNC, wall volume, lumen volume, PWV and the changes of blood lipid parameters (TC, LDL-C, HDL-C and TG) in 3 and 24 months (P>0.05). Conclusion: Lipid-lowering therapy possesses different effects on carotid atherosclerotic plaque in diabetic and non-diabetic patients, and the LRNC improvement is more significant in non-diabetic patients as compared to diabetic patients.
Carotid Arteries/pathology* ; Carotid Artery Diseases/drug therapy* ; Cholesterol, HDL/therapeutic use* ; Cholesterol, LDL ; Diabetes Mellitus ; Humans ; Magnetic Resonance Imaging/methods* ; Necrosis/pathology* ; Plaque, Atherosclerotic/drug therapy* ; Retrospective Studies ; Rosuvastatin Calcium/therapeutic use*

INTRODUCTION: In recent years, () has emerged as the predominant cause of pyogenic liver abscess in Asia. - as the causative microorganism in other visceral organ abscesses-is less described. In this study, we seeked to describe the clinical characteristics of visceral organ abscesses in our institution and evaluated the prescription practices of physicians with regard to antibiotic therapy. MATERIALS AND METHODS: A retrospective analysis of patients with culture positive (blood or abscess aspirate) visceral organ abscesses from May 2014 to April 2016 requiring hospitalisation in Changi General Hospital was conducted. RESULTS: A total of 140 adult patients with visceral organ abscesses were identified. The commonest site of involvement was the liver (77.9%), followed by genitourinary tract (20.7%). Diabetic patients were more likely to have liver abscesses, genitourinary abscesses, abscesses in 2 or more organs, genitourinary disease with abscess formation outside of the genitourinary tract, and endovascular infection. Patients with extended spectrum beta-lactamase producing , were more likely to have an obstructive lesion related to the site of the abscess. Overall mortality rate was 7.1%. Amongst survivors, the mean total duration of parenteral antimicrobial therapy was 2.5 weeks before switching to oral antimicrobial agents. CONCLUSION Genitourinary tract is the commonest extra-hepatic site for visceral organ abscess in infections. Parenteral to oral switch of antimicrobial agents appears to be a safe and effective treatment option.
Abscess ; classification ; microbiology ; mortality ; therapy ; Anti-Bacterial Agents ; therapeutic use ; Diabetes Mellitus ; epidemiology ; Female ; Humans ; Klebsiella pneumoniae ; isolation & purification ; Liver ; pathology ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Singapore ; epidemiology ; Survival Analysis ; Urogenital System ; pathology ; Viscera ; pathology

Ossification of the posterior longitudinal ligament (OPLL) can be defined as an ectopic ossification in the tissues of spinal ligament showing a hyperostotic condition. OPLL is developed mostly in the cervical spine and clinical presentations of OPLL are majorly myelopathy and/or radiculopathy, with serious neurological pathology resulting in paralysis of extremities and disturbances of motility lowering the quality of life. OPLL is known to be an idiopathic and multifactorial disease, which genetic factors and non-genetic factors including diet, obesity, physical strain on the posterior longitudinal ligament, age, and diabetes mellitus, are involved into the pathogenesis. Up to now, surgical management by decompressing the spinal cord is regarded as standard treatment for OPLL, although there might be the risk of development of reprogression of ossification. The molecular pathogenesis and efficient therapeutic strategy, especially pharmacotherapy and/or preventive intervention, of OPLL has not been clearly elucidated and suggested. Therefore, in this review, we tried to give an overview to the present research results on OPLL, in order to shed light on the potential pharmacotherapy based on molecular pathophysiologic aspect of OPLL, especially on the genetic/genomic factors involved into the etiology of OPLL.
Diabetes Mellitus ; Diet ; Drug Therapy ; Extremities ; Ligaments ; Longitudinal Ligaments ; Obesity ; Ossification, Heterotopic ; Paralysis ; Pathology ; Quality of Life ; Radiculopathy ; Spinal Cord ; Spinal Cord Diseases ; Spine

Xiao Ke Qing (XKQ) granule has been clinically used to treat type 2 diabetes mellitus (T2DM) for 10 years in Chinese traditional medication. However, its mechanisms against hyperglycemia remain poorly understood. This study aims to investigate XKQ mechanisms on diabetes and diabetic liver disease by using the KKAy mice model. Our results indicate that XKQ can significantly reduce food and water intake. XKQ treatment also remarkably decreases both the fasting blood glucose and blood glucose in the oral glucose tolerance test. Additionally, XKQ can significantly decrease the serum alanine aminotransferase level and liver index and can alleviate the fat degeneration in liver tissues. Moreover, XKQ can ameliorate insulin resistance and upregulate the expression of IRS-1, PI3K (p85), p-Akt, and GLUT4 in the skeletal muscle of KKAy mice. XKQ is an effective drug for T2DM by ameliorating insulin resistance and regulating the PI3K/Akt signaling pathway in the skeletal muscle.
Animals ; Blood Glucose ; drug effects ; metabolism ; Diabetes Mellitus, Type 2 ; drug therapy ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glucose Tolerance Test ; Glucose Transporter Type 4 ; metabolism ; Hypoglycemic Agents ; pharmacology ; Insulin ; blood ; Insulin Resistance ; Liver ; drug effects ; pathology ; Mice ; Mice, Inbred C57BL ; Phosphatidylinositol 3-Kinases ; metabolism ; Proto-Oncogene Proteins c-akt ; metabolism ; Signal Transduction ; drug effects

Objective: To investigate the correlation of intermittent androgen-deprivation therapy (IADT) and continuous androgen-deprivation therapy (CADT) for advanced prostate cancer (PCa) with the risks of secondary diabetes mellitus (DM) and impaired glucose tolerance (IGT). METHODS: We conducted a retrospective case-control study of the advanced PCa patients treated by IADT or CADT in our hospital from January 2013 to December 2015. Based on the levels fasting blood glucose and 2-hour postprandial blood glucose, results of oral glucose tolerance test, and clinical symptoms of the patients, we statistically analyzed the IADT- or CADT-related risk factors for DM and IGT and the relationship of the body mass index (BMI), hypertension, smoking, and alcohol consumption with secondary DM and IGT. RESULTS: IADT was given to 53 (46.5%) of the patients, aged (69.1 ± 4.3) years, and CADT to 61 (53.5%), aged (70.2 ± 5.7) years. No statistically significant differences were observed in clinical characteristics between the two groups of patients (P > 0.05). BMI, blood pressure, smoking and drinking exhibited no significant influence on the development of DM or IGT either in the IADT (P > 0.05) or the CADT group. The incidence of IGT was significantly lower in the IADT than in the CADT group (P = 0.03), but that of DM showed no statistically significant difference between the two groups (P = 0.64). CONCLUSIONS Compared with CADT, IADT has a lower risk of IGT and a higher safety in the treatment of advanced prostate cancer.
Aged ; Alcohol Drinking ; adverse effects ; Androgen Antagonists ; adverse effects ; therapeutic use ; Blood Glucose ; metabolism ; Body Mass Index ; Case-Control Studies ; Diabetes Mellitus ; chemically induced ; Glucose Intolerance ; chemically induced ; Glucose Tolerance Test ; Humans ; Hypertension ; complications ; Male ; Prostatic Neoplasms ; drug therapy ; pathology ; Retrospective Studies ; Risk Factors ; Smoking ; adverse effects

PURPOSE: Diabetic nephropathy is a serious complication of type 2 diabetes mellitus, and delaying the development of diabetic nephropathy in patients with diabetes mellitus is very important. In this study, we investigated inflammation, oxidative stress, and lipid metabolism to assess whether curcumin ameliorates diabetic nephropathy. MATERIALS AND METHODS: Animals were divided into three groups: Long-Evans-Tokushima-Otsuka rats for normal controls, Otsuka-Long-Evans-Tokushima Fatty (OLETF) rats for the diabetic group, and curcumin-treated (100 mg/kg/day) OLETF rats. We measured body and epididymal fat weights, and examined plasma glucose, adiponectin, and lipid profiles at 45 weeks. To confirm renal damage, we measured albumin-creatinine ratio, superoxide dismutase (SOD), and malondialdehyde (MDA) in urine samples. Glomerular basement membrane thickness and slit pore density were evaluated in the renal cortex tissue of rats. Furthermore, we conducted adenosine monophosphate-activated protein kinase (AMPK) signaling and oxidative stress-related nuclear factor (erythroid-derived 2)-like 2 (Nrf2) signaling to investigate mechanisms of lipotoxicity in kidneys. RESULTS: Curcumin ameliorated albuminuria, pathophysiologic changes on the glomerulus, urinary MDA, and urinary SOD related with elevated Nrf2 signaling, as well as serum lipid-related index and ectopic lipid accumulation through activation of AMPK signaling. CONCLUSION: Collectively, these findings indicate that curcumin exerts renoprotective effects by inhibiting renal lipid accumulation and oxidative stress through AMPK and Nrf2 signaling pathway.
Albuminuria ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Curcumin/*pharmacology ; Diabetes Mellitus, Type 2/*metabolism/urine ; Diabetic Nephropathies/complications/*drug therapy/metabolism/pathology ; Gene Expression/drug effects ; Inflammation ; Kidney/drug effects/metabolism/physiopathology ; Kidney Glomerulus/metabolism/physiopathology ; Lipid Metabolism/*drug effects ; Male ; Malondialdehyde/metabolism/urine ; Oxidative Stress/*drug effects ; Rats ; Rats, Inbred OLETF ; Rats, Long-Evans ; Superoxide Dismutase/metabolism

This article aimed at exploring the effects and protective mechanism of β-CM7 on renin angiotensin system (RAS) in diabetic rats myocardial tissue. We divided 32 male SD rats into 4 groups: control group, diabetic model control group, insulin (3.7x10(-8) mol/d) treatment group and β-CM7 (7.5x10(-8) mol/d) treatment group. After 30 days, all rats were decapitated and myocardical tissues were collected immediately. After injection, β-CM7 could decrease the content of Ang II, increase the content of Angl-7. And β-CM7 could improve the mRNA of AT1 receptor and Mas receptor. β-CM7 also could improve the mRNA of ACE and ACE2, enhance the activity of ACE and ACE2. These data confirmed tli β-CM7 could activate ACE2-Angl-7-Mas axis, negative passage in RAS, to inhibit the expression ACE mnRiJA and protein in rat myocardium, alleviate the myocardial tissue damage induced by Ang II. The effect of β-CM7 on inhibiting myocardium damage might be related to ACE/ACE2 passageway.
Angiotensin II ; metabolism ; Animals ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetic Cardiomyopathies ; drug therapy ; Endorphins ; pharmacology ; Male ; Myocardium ; metabolism ; pathology ; Peptide Fragments ; pharmacology ; Peptidyl-Dipeptidase A ; metabolism ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Receptor, Angiotensin, Type 1 ; metabolism ; Receptors, G-Protein-Coupled ; metabolism ; Renin-Angiotensin System