Comparison of the Effects of Mitiglinide and Glibenclamide Administered in Combination with the Dipeptidyl Peptidase-IV Inhibitor Sitagliptin in Rats with Streptozotocin-Nicotinamide-Induced Type 2 Diabetes

Drug Research ◽  
2017 ◽  
Vol 67 (07) ◽  
pp. 396-403 ◽  
Author(s):  
Kenji Akahane ◽  
Kazuma Ojima ◽  
Ayaka Yokoyama ◽  
Toshihiro Inoue ◽  
Sumiyoshi Kiguchi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dpp Iv

Abstract We compared the individual effects of mitiglinide and glibenclamide administered in combination with the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin on plasma DPP-IV activity and blood glucose levels in rats with streptozotocin-nicotinamide-induced type 2 diabetes (STZ-NA rats). We examined the inhibitory activity of mitiglinide and glibenclamide as well as their combination with sitagliptin on plasma DPP-IV activity in STZ-NA rats. The oral glucose tolerance test (OGTT) was used to compare effects of mitiglinide, glibenclamide, and their combination with sitagliptin on blood glucose levels in STZ-NA rats. Mitiglinide and glibenclamide did not inhibit rat DPP-IV and did not influence the inhibitory effect of sitagliptin on rat plasma DPP-IV activity. In STZ-NA rats, plasma glucose levels were stronger suppressed by a combination of mitiglinide and sitagliptin than by either drug used alone. However, no clear effect of the combination of glibenclamide and sitagliptin was observed. These results indicate that the combination of mitiglinide and sitagliptin has a lower risk of hypoglycemia in the rats with induced type 2 diabetes compared with the combination of glibenclamide and sitagliptin. The combination of mitiglinide and sitagliptin can be a promising combination for the treatment of diabetic patients.

scholarly journals Study on the prevalence of dyslipidemia in type 2 diabetes mellitus

2019 ◽  
Vol 6 (3) ◽  
pp. 786
Author(s):  
Eda Dayakar ◽  
C. Sathya Sree ◽  
E. Sanjay
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Type 2 Diabetic

Background: Diabetes mellitus is a common health problem globally. Dyslipidaemia is a major risk factor to develop cardiovascular disease in diabetics. They present study was undertaken to find out the prevalence of dyslipidaemia in type 2 diabetic patients.Methods: The present study was a cross sectional study consisting of 46 (23 male and 23 female) known type 2 diabetes mellitus patients. Age, gender, duration of diabetes, body mass index (BMI) was recorder in all the diabetic patients.  Fasting blood glucose levels, total cholesterol, triglycerides, HDL, LDL, VLDL levels were measured using standard methods and recorded.Results: The average total cholesterol, triglycerides, LDL, HDL and VLDL were 200±42mg/dl, 169.62±89.79mg/dl, 132.45±36.38mg/dl,39.1±16.6mg/dl and 35.85±17.09mg/dl respectively. The incidence of occurrence of hypercholesterolemia was 58.6% and hypertriglyceridemia 36.9%. Increased levels of LDL were observed in 30 (65.2%) patients and reduced HDL was observed in 43 (93.4%) patients. The incidence rate of dyslipidaemia was higher in female diabetic patients when compared to male diabetic patients.Conclusions: Awareness on the dyslipidaemia and its risk factors should be provided to the type 2 diabetic patients as they are more prone to get cardiovascular disease and lipid profile also should be monitored regularly along with blood glucose levels.

scholarly journals Relevance of Uric Acid in Progression of Type 2 Diabetes Mellitus

2010 ◽  
Vol 10 (1) ◽  
pp. 54-59 ◽  
Author(s):  
Adlija Čaušević ◽  
Sabina Semiz ◽  
Amra Macić-Džanković ◽  
Bakira Cico ◽  
Tanja Dujić ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Uric Acid ◽  
Risk Factor ◽  
Blood Glucose ◽  
Genetic Effect ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Liver And Kidney

Recent studies have introduced serum uric acid (UA) as a potential risk factor for developing diabetes, hypertension, stroke, and cardiovascular diseases. The value of elevated levels of UA in serum as a risk factor for diabetes development is still under scrutiny. Recent data suggest that clearance of UA is being reduced with increase in insulin resistance and UA as a marker of prediabetes period. However, conflicting data related to UA in serum of patients with Type 2 diabetes prompted us to study the urine/serum ratio of UA levels (USRUA) in these patients and healthy controls. All subjects included in the study were free of evidence of hepatitis B or C viral infection or active liver and kidney damage. Patients receiving drugs known to influence UA levels were also excluded from this study. Analysis of glucose and uric acid were performed on Dade Behring analyzer using standard IFCC protocols. Interestingly, our data demonstrated about 2.5 fold higher USRUA values in diabetic patients as compared to control subjects. Furthermore, there was a trend of correlation of USRUA value with the blood glucose levels in diabetic patients, which was more prominent in diabetic men than in women. With aging, levels of uric acid increased in serum of diabetic patients, and this effect was also more profound in male than in female diabetics. In conclusion, this study showed significantly elevated USRUA levels in patients with Type 2 diabetes, a negative USRUA correlation with the blood glucose levels in diabetic patients, and an effect of sex and age on the uric acid levels. Since literature data suggest a strong genetic effect on UA levels, it would be pertinent to perform further, possibly genetic studies, in order to clarify gender and ethnic differences in UA concentrations.

scholarly journals Enhanced Plasma H2S Levels Associated With Fasting Blood Glucose In Type-2 Diabetes Mellitus

2015 ◽  
Vol 6 (6) ◽  
pp. 11-15 ◽  
Author(s):  
Pinaki Saha ◽  
Piyasa Banerjee ◽  
Prasenjit Pal ◽  
Lakshmisona Auddya ◽  
Santanu Sen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Patients ◽  
Glucose Levels ◽  
Blood Glucose Levels

Introduction: A number of recent literatures suggest a potential role of H2S and H2S modifying agents in the etiology and management of type-2 diabetes mellitus. Objective: The current study was aimed to evaluate the plasma levels of H2S in the patients with type 2 Diabetes mellitus and to find out if there is any relationship of H2S concentrations with the fasting blood glucose levels. Methods: Plasma H2S levels were measured in sixty two recently diagnosed type 2 diabetic patients and compared with similar number of healthy volunteers as controls. Results: The plasma H2S level in the patients ( 81.17 ± 16.40 micromol/l ) is significantly higher (P< 0.001) than the healthy controls (50.69 ± 8.69 micromol/l) and the H2S levels in plasma have significant positive correlation (r= 0.359, P=0.004) with fasting blood glucose levels. Conclusion: The present study has elucidated that the patients with type-2 diabetes mellitus are associated with elevated plasma H2S levels which are well correlated with glucose levels. This reveals a potential the role of H2S modulators towards the management of this non-communicable epidemic disorder. DOI: http://dx.doi.org/10.3126/ajms.v6i6.12532Asian Journal of Medical Sciences Vol.6(6) 2015 11-15

scholarly journals Insulinotropic actions of nateglinide in type 2 diabetic patients and effects on dipeptidyl peptidase-IV activity and glucose-dependent insulinotropic polypeptide degradation

2009 ◽  
Vol 161 (6) ◽  
pp. 877-885 ◽  
Author(s):  
Aine M McKillop ◽  
Nicola A Duffy ◽  
John R Lindsay ◽  
Brian D Green ◽  
S Patterson ◽  
...  
Keyword(s):  
Dipeptidyl Peptidase ◽  
Inhibitory Effect ◽  
Dipeptidyl Peptidase Iv ◽  
Oral Glucose ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Dpp Iv ◽  
Type 2 Diabetic

BackgroundNateglinide restores early-phase insulin secretion to feeding and reduces postprandial hyperglycaemia in type 2 diabetes. This study evaluated the effects of nateglinide on dipeptidyl peptidase-IV (DPP-IV) activity and glucose-dependent insulinotropic polypeptide (GIP) degradation.Research design and methodsBlood samples were collected from type 2 diabetic subjects (n=10, fasting glucose 9.36±1.2 mmol/l) following administration of oral nateglinide (120 mg) 10 min prior to a 75 g oral glucose load in a randomised crossover design.ResultsPlasma glucose reached 18.2±1.7 and 16.7±1.7 mmol/l at 90 min in control and placebo groups (P<0.001). These effects were accompanied by prompt 32% inhibition of DPP-IV activity after 10 min (19.9±1.6 nmol/ml per min, P<0.05), reaching a minimum of 1.9±0.1 nmol/ml per min at 120 min (P<0.001) after nateglinide. Insulin and C-peptide levels increased significantly compared with placebo, to peak after 90 min at 637.6±163.9 pmol/l (P<0.05) and 11.8±1.4 mg/l (P<0.01) respectively. DPP-IV-mediated degradation of GIP was significantly less in patients receiving nateglinide compared with placebo. Inhibition of DPP-IV activity corresponded with a time- and concentration-dependent inhibitory effect of nateglinide on DPP-IV-mediated truncation of GIP(1–42) to GIP(3–42) in vitro. Comparison of in vitro inhibition of DPP-IV by nateglinide and vildagliptin revealed IC50 values of 17.1 and 2.1 μM respectively.ConclusionsAlthough considerably less potent than specified DPP-IV inhibitors, the possibility that some of the beneficial actions of nateglinide are indirectly mediated through DPP-IV inhibition and increased bioavailability of GIP and other incretins merits consideration.

scholarly journals Fasting and Post Prandial Monitoring of Dipeptidyl Peptidase-IV (DPP-IV) - A Biomarker to Assess Incretin Response in Type-2 Diabetes

2010 ◽  
Vol 2 (2) ◽  
pp. 81-85
Author(s):  
Venkatesham Allenki ◽  
Rama Krishna Devarakonda ◽  
Rama Narsimha Reddy Anreddy ◽  
Narayana Pantam ◽  
Narsimha Reddy Yellu
Keyword(s):  
Type 2 Diabetes ◽  
Glycosylated Hemoglobin ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Diabetic Patients ◽  
Sudden Increase ◽  
Dpp Iv ◽  
Diabetes Status ◽  
Type 2 Diabetic

Dipeptidyl peptidase-IV (DPP-IV) could serve as a potential biomarker in monitoring the disease progression and improvement on treatment. To investigate fasting & post prandial response of DPP-IV enzyme as indirect marker of incretin response failure after chronic treatment with metformin in type 2 diabetes. The study included twelve nondiabetic subjects, ten patients with glycosylated hemoglobin values (6-8%) and fifteen patients with glycosylated hemoglobin greater than 8 % of type-2 diabetes patients of either sex with metformin treatment above 3 years were recruited. Fasting and post prandial DPP-IV levels were calculated. HbA1c was used to assess diabetes status. DPP-IV activity (fasting) in type 2 diabetic subjects with HbA1c > 8 % was significantly higher DPP-IV (44.67 ± 2.19 U/l) than in non diabetic subjects (24.39 ± 3.97 U/l). A significant correlation between DPP-IV (fasting / post prandial) and HbA1c (r = 0.821 & r = 0.732, P< 0.01) was observed in both diabetic (HbA1c 6-8, HbA1c < 8) patients. Hyperglycemia induces significant increase in serum DPP-IV activity in fasting condition and might contribute to the reduction in active glucagon like peptide-1(GLP-1) in type 2 diabetic subjects. In normal subjects during post prandial condition, there is sudden increase followed by decrease of GLP-1 due to cleavage of GLP-1 to as substrate of DPP-IV is seen as upsurge of DPP-IV. This response was lacking in diabetic patients with high HbA1c indicates indirectly metformin failure to secrete GLP-1. High fasting level and decreased post prandial of DPP-IV may indicate drug failure in type-2 diabetes mellitus.  Key words: Type 2 diabetes; metformin; DPP-IV; HbA1c; GLP-1.DOI: 10.3329/sjps.v2i2.1698Stamford Journal of Pharmaceutical Sciences Vol.2(2) 2009: 81-85

Recent medicinal chemistry approach for development of dipeptidyl peptidase IV inhibitors

2020 ◽  
Vol 27 ◽  
Author(s):  
Bhumi M. Shah ◽  
Palmi Modi ◽  
Priti Trivedi
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Blood Glucose Level ◽  
Insulin Release ◽  
Glucose Level ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Dpp Iv ◽  
Glucose Output

Background: Diabetes, a metabolic disease occurs due to decrease or no effect of insulin on blood glucose level. Current oral medication stimulates insulin release, increase glucose absorption and its utilization as well decrease hepatic glucose output. Two major incretin hormones like Glucose dependent insulinotropic polypeptide (GIP) and glucagon like peptide – 1 (GLP -1) stimulate insulin release after meal but their action is inhibited by enzyme dipeptidyl peptidase- IV. Objective: The activity of endogenous GLP-1 and GIP prolong and extend with DPP IV inhibitors which are responsible for stimulation of insulin secretion and regulate blood glucose level. DPP IV inhibitors have shown effectiveness and endurability with neutral effect on weight as well as less chances of hypoglycemia in management of type 2 diabetes. These journeys have been started from Sitagliptin (marketed in 2006) to Evogliptin (marketed in 2015, Korea). Conclusion: Treatment of type 2 diabetes includes lifestyle changes, oral medications, and insulin. Newer and superior therapies are required than presently prescribed drugs. Various heterocyclic derivatives have been tried but due to masking of DASH proteins, CYP enzymes and hERG channel, they showed side effects. Based on these, study has been focused on the development of safe, influential, selective and long-lasting inhibitors of DPP IV.

scholarly journals Expression and Characterization of a Potent Long-Acting GLP-1 Receptor Like Agonist, Exendin-4-Fc

2021 ◽  
Author(s):  
Wen Zhang ◽  
Ming Li ◽  
Yanlu Zan ◽  
Yi Bai
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Half Life ◽  
Ovary Cell ◽  
Oral Glucose ◽  
Dependent Manner ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Long Acting

AbstractHuman GLP-1 (glucagon-like peptide-1) can produce a remarkable improvement in glycemic control in patients with type 2 diabetes. However, its clinical benefits are limited by its short half-life, which is less than 2 min because of its small size and rapid enzymatic inactivation by dipeptidyl peptidase IV. We engineered Exendin-4-Fc, a 66-kDa fusion protein by linking an IgG2 Fc to Exendin-4. A stably transfected Chinese hamster ovary cell line was obtained using electroporation. Exendin-4-Fc stimulated insulin secretion in INS-1 cells in a dose- and glucose-dependent manner and increased insulin mRNA expression. The plasma half-life of Exendin-4-Fc in cynomolgus monkeys was approximately 133.92 ± 25.1 h. In the KKAy mouse model of diabetes, one intraperitoneal injection of Exendin-4-Fc (1 mg/kg) reduced blood glucose levels for 5 days. A 4-week repeat-administration study identified sustained effects on blood glucose levels. Oral glucose tolerance tests conducted at the beginning and end of this 4-week period showed that Exendin-4-Fc produced a stable glucose lowering effect. In addition, KKAy mice treated with Exendin-4-Fc showed statistically significant weight loss from day 23. In conclusion, these properties of Exendin-4-Fc demonstrated that it could be a potential long-acting GLP-1 receptor agonist for the treatment of type 2 diabetes.

Efeitos dos Programas de Treinamento Aeróbio, de Força e Combinado na Glicose Sanguínea em Diabéticos do Tipo 2: uma Revisão Sistemática/ Effects of Aerobic, Strength and Combined Programs Training on Blood Glucose in Type 2 Diabetic: a Systematic Review.

1970 ◽  
Vol 5 (1) ◽  
pp. 61-74 ◽  
Author(s):  
Alexandre de Souza E Silva ◽  
Maria Paula Gonçalves Mota
Keyword(s):  
Diabetes Mellitus ◽  
Systematic Review ◽  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Training Program ◽  
Aerobic Training ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Pubmed Database

O trabalho tem como objetivo analisar os estudos que avaliaram os efeitos dos programas de treinamento aeróbio, força e combinado nos níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Foi utilizado o método de revisão sistemática, sendo utilizada a base de dados PubMed. As palavras chaves utilizadas para pesquisa foram training and diabetes. Foram identificados 484 artigos originais. Apenas 17 estudos respeitaram os critérios de inclusão. Os resultados evidenciam que os programas de treinamento aeróbio diminuíram os níveis de glicose. O programa de treinamento de força também foi favorável à diminuição dos níveis de glicose sanguínea. Já o programa de treinamento combinado não demonstrou efeitos favoráveis no controle da glicose sanguínea. Conclui-se que o programa de treinamento aeróbio e de força ajudam a controlar os níveis de glicose sanguínea em indivíduos com diabetes do tipo 2. Palavras-chave: diabetes mellitus, treinamento, glicose.ABSTRACTThe study aims to analyze the studies that evaluated the effects of aerobic, strength and combined programs training in blood glucose levels in people with type 2 diabetes. We used a systematic review method and is used to PubMed database. The key words used for searching were training and diabetes. We identified 484 original articles. Only 17 studies complied with the inclusion criteria. The results show that aerobic training programs decreased glucose levels. The strength training program was also favorable to decrease in blood glucose levels. But the combined training program has not shown favorable effects on blood glucose control. We conclude that the aerobic training and strength helps control blood glucose levels in individuals with type 2 diabetes. Keywords: diabetes mellitus, training, glucose.

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