Treatment of Type 2 Diabetes with a Combination of Two Insulin Sensitizers. Increased Efficacy and Fewer Side-effects

2004 ◽  
Vol 1 (1) ◽  
pp. 29-33
Author(s):  
David SH Bell
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Insulin Sensitizers

PPARγ: Potential Therapeutic Target for Ailments Beyond Diabetes and its Natural Agonism

2019 ◽  
Vol 20 (12) ◽  
pp. 1281-1294 ◽  
Author(s):  
Sana Shafi ◽  
Pawan Gupta ◽  
Gopal Lal Khatik ◽  
Jeena Gupta
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Therapeutic Target ◽  
Bone Fractures ◽  
Ppar Gamma ◽  
Disease States ◽  
Insulin Sensitizers ◽  
Cord Injury ◽  
Agonistic Activity

Intense research interests have been observed in establishing PPAR gamma as a therapeutic target for diabetes. However, PPARγ is also emerging as an important therapeutic target for varied disease states other than type 2 diabetes like neurodegenerative disorders, cancer, spinal cord injury, asthma, and cardiovascular problems. Furthermore, glitazones, the synthetic thiazolidinediones, also known as insulin sensitizers, are the largely studied PPARγ agonists and the only ones approved for the treatment of type 2 diabetes. However, they are loaded with side effects like fluid retention, obesity, hepatic failure, bone fractures, and cardiac failure; which restrict their clinical application. Medicinal plants used traditionally are the sources of bioactive compounds to be used for the development of successful drugs and many structurally diverse natural molecules are already established as PPARγ agonists. These natural partial agonists when compared to full agonist synthetic thiazolidinediones led to weaker PPARγ activation with lesser side effects but are not thoroughly investigated. Their thorough characterization and elucidation of mechanistic activity might prove beneficial for counteracting diseases by modulating PPARγ activity through dietary changes. We aim to review the therapeutic significance of PPARγ for ailments other than diabetes and highlight natural molecules with potential PPARγ agonistic activity.

Efficacy and cardiovascular safety of Thiazolidinediones

2020 ◽  
Vol 15 ◽  
Author(s):  
Raveendran Arkiath Veettil ◽  
Cornelius James Fernandez ◽  
Koshy Jacob
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Glucose Transporter ◽  
Cell Function ◽  
Cardiovascular Safety ◽  
Cardiovascular Outcome Trials ◽  
Glucose Transporter 2 ◽  
Insulin Sensitizers

: Type 2 diabetes mellitus (T2DM) is characterized by a progressive beta cell dysfunction in the setting of peripheral insulin resistance. Insulin resistance in subjects with type 2 diabetes and metabolic syndrome is primarily caused by an ectopic fat accumulation in liver and skeletal muscle. Insulin sensitizers are particularly important in the management of T2DM. Though, thiazolidinediones (TZDs) are principally insulin sensitizers, they possess an ability to preserve pancreatic β-cell function and thereby exhibit durable glycemic control. Cardiovascular outcome trials (CVOTs) have shown that Glucagon-like-peptide 1 receptor agonists (GLP-1 RAs) and sodium glucose transporter-2 inhibitors (SGLT2i) have proven cardiovascular safety. In this era of CVOTs, drugs with proven cardiovascular (CV) safety are often preferred in patients with preexisting cardiovascular disease or at risk of cardiovascular disease. In this review, we will describe the three available drugs belonging to the TZD family, with special emphasis on their efficacy and CV safety.

Effectiveness and side effects of thiazolidinediones for type 2 diabetes

2005 ◽  
Vol 182 (9) ◽  
pp. 492-494 ◽  
Author(s):  
Nirusha Arnold ◽  
Mark McLean ◽  
David R Chipps ◽  
N Wah Cheung
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects

scholarly journals Pseudoginsenoside F11, a Novel Partial PPARγAgonist, Promotes Adiponectin Oligomerization and Secretion in 3T3-L1 Adipocytes

PPAR Research ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Guoyu Wu ◽  
Junyang Yi ◽  
Ling Liu ◽  
Pengcheng Wang ◽  
Zhijie Zhang ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Side Effects ◽  
Hormone Receptor ◽  
Adipocyte Differentiation ◽  
American Ginseng ◽  
Nuclear Hormone Receptor ◽  
Targeted Therapeutics ◽  
Panax Quinquefolium ◽  
Master Regulator

PPARγis a nuclear hormone receptor that functions as a master regulator of adipocyte differentiation and development. Full PPARγagonists, such as the thiazolidinediones (TZDs), have been widely used to treat type 2 diabetes. However, they are characterized by undesirable side effects due to their strong agonist activities. Pseudoginsenoside F11 (p-F11) is an ocotillol-type ginsenoside isolated fromPanax quinquefolium L.(American ginseng). In this study, we found that p-F11 activates PPARγwith modest adipogenic activity. In addition, p-F11 promotes adiponectin oligomerization and secretion in 3T3-L1 adipocytes. We also found that p-F11 inhibits obesity-linked phosphorylation of PPARγat Ser-273 by Cdk5. Therefore, p-F11 is a novel partial PPARγagonist, which might have the potential to be developed as a new PPARγ-targeted therapeutics for type 2 diabetes.

Abstract 234: Treatment Satisfaction Levels among Adults with Concomitant Conditions of Type 2 Diabetes Mellitus and Hypertension

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Kathleen M Fox ◽  
Susan Grandy ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Side Effects ◽  
Diabetes Medication ◽  
Medication Therapy ◽  
The Us ◽  
Medication Side

Objective: This investigation evaluated the satisfaction with therapy for adults with the concomitant conditions of type 2 diabetes mellitus (T2DM) and hypertension (HTN). Methods: Respondents to the US S tudy to H elp I mprove E arly evaluation and management of risk factors L eading to D iabetes (SHIELD) 2009 survey reported their disease conditions, current medications, and satisfaction with therapy. Respondents reporting T2DM with concomitant HTN were identified. Current medications were catalogued, as respondents referred to their prescription bottles to record the name of each medication. Therapy satisfaction was captured with 3 separate questions as satisfaction/dissatisfaction with: 1) ability of the medication to prevent or treat your condition, 2) side effects of the medication, and 3) the medication overall; and scored using a 0 (completely dissatisfied) to 5 (completely satisfied) scale for heart disease treatment and diabetes treatment, separately. Scores of 0-2 were categorized as dissatisfied, score of 3 was neutral and scores 4-5 were satisfied. Results: A total of 911 adults with T2DM and HTN reported their satisfaction with therapy. For those who were dissatisfied with their diabetes medication (n = 63), 52.6% were also dissatisfied with their heart disease medication's ability to treat their HTN, 64.5% were dissatisfied with the side effects of their heart medications, and 61.9% were dissatisfied with their heart medication overall. For those who were dissatisfied with their heart disease medication (n = 59), 74.5% were also dissatisfied with their diabetes medication's ability to treat their diabetes, 56.6% were dissatisfied with the side effects of their diabetes medication, and 66.1% were dissatisfied with their diabetes medication overall. Conclusions: Although most respondents with T2DM and HTN were satisfied with their treatment, dissatisfaction with treatment for one condition was associated with therapy dissatisfaction in the other condition. Approximately 53%-65% of respondents who were dissatisfied with their diabetes medication were also dissatisfied with their HTN medication overall and in the ability to treat the condition and medication side effects.

scholarly journals Oxidative stress in patients with type 2 diabetes mellitus treated with metformin

2017 ◽  
Vol 27 (2) ◽  
pp. 25857
Author(s):  
Samuel Selbach Dries ◽  
Bárbara Da Silveira Soares ◽  
Ana Luiza Ziulkoski ◽  
Simone Gasparin Verza ◽  
Rafael Linden ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Superoxide Dismutase ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Side Effects ◽  
Diabetic Complications

*** Oxidative stress in patients with type 2 diabetes mellitus treated with metformin ***AIMS: To evaluate oxidative stress parameters in patients with type 2 diabetes mellitus treated with metformin, relating these values to its side effects, plasma levels, glycemic control, diabetic complications, lipid profile, and the influence of pharmacotherapeutic follow-up.METHODS: Patients with type 2 diabetes mellitus, on metformin and in pharmacotherapeutic follow-up for four months, were evaluated. The pharmacotherapeutic follow-up consisted in providing information and answering patients’ questions about medication and disease. In addition, administration times, dosages, and presence or absence of side effects related to the use of metformin were verified. Glycemic and lipid profile, oxidative stress (superoxide dismutase and malondialdehyde) and plasma metformin were evaluated. Pearson’s correlation and Spearman’s correlation were performed to evaluate the relationship between the variables at the beginning of the study. The independent t-test and Mann-Whitney U test were used to assess the difference between the groups with and without diabetic complications. The range of values between the beginning and  end of the study was evaluated using Student’s t-test or Wilcoxon U test. The significance level was set at 5%.RESULTS: The initial sample consisted of 49 patients aged 59±9 years with a body mass index of 29.8±5.1 kg/m2, who have had diabetes for a median time of 36 months (interquartile range of 1-240) and have been on metformin for a median time of 36 months (interquartile range of 1-180). Twenty-five patients left the study between the second and fourth meetings. Malondialdehyde levels differed between before and after pharmacotherapeutic follow-up, being positively correlated with blood glucose, glycohemoglobin, and triglyceride level, and negatively correlated with metformin and superoxide dismutase. Blood glucose, glycohemoglobin, and malondialdehyde levels increased, whereas metformin levels decreased in the group with diabetic complications, and there was a correlation between malondialdehyde and the number of diabetic complications per patient.CONCLUSIONS: In this sample of patients with type 2 diabetes mellitus treated with metformin, oxidative stress was more pronounced in those with poor glycemic control and diabetic complications.

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

Sign in / Sign up

Export Citation Format

Share Document