scholarly journals Glycemic and Non-Glycemic Effects of Teneligliptin

2020 ◽  
pp. 51-63
Author(s):  
Ranakishor Pelluri ◽  
Kongara Srikanth ◽  
Jithendra Chimakurthy ◽  
Rasheed Ahemad Shaik ◽  
R. Lavanya ◽  
...  
Keyword(s):  
Vascular Complications ◽  
Intestinal Secretion ◽  
Dipeptidyl Peptidase ◽  
Vital Role ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Vascular Protection ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Anti Inflammatory

The gut enzymes are released in response to intake of meal, those are GLP-I (glucagon link peptide-I) & GIP (glucose-dependent insulin tropic polypeptide) along with DPP-4(Dipeptidyl peptidase-4). GLP-I has vital role in control of glucose levels and it may also has capacity reduce body weight and it can manage some micro & macro-vascular complications. Unfortunately it has very shorter half-life 1-2 min, and eventually it was degraded by DPP-4 enzyme.  Therefore GLP-I has ineffective to perform its tasks. To overcome this incidence essential to inhibit DPP-4 enzyme is benefited in diabetics and in non diabetics suffering with micro, macro vascular complications. Ubiquitous Dipeptidyl peptidase (DPP) - 4 has pleiotropic effects because it is widely distributed other than intestine. DPP-4 enzyme inhibition has a promising effect on glycemic control. DPP-4 inhibition is also involved in the improvement of non-glycemic effects as directly or indirectly the DPP-4 enzyme is linked with some pathological conditions of particular organs, such as DPP-4 is linked with the intestinal secretion of triglycerides, and DPP-4 is expressed in the glomerulus in uncontrolled diabetics which in turn leads to nephritis. DPP-4 release strongly correlates with adipocyte size, potentially representing an important source of DPP-4 in obesity. DPP-4 inhibition produces an anti-inflammatory activity because the activity of DPP-4 results in reduced production of cytokines including interleukins and interferon-G. All these anti-inflammatory agents are inhibited by the DPP-4 enzyme which can lead to pathogenesis of cardiovascular diseases and provokes atherosclerosis & psoriasis. Serum sodium and brain natriuretic peptide (BNP) levels are also regulated by inhibition of the DPP-4 enzyme and which can produce vascular protection & regulates blood pressure. Teneligliptin is a recently developed oral DPP-4 inhibitor indicated for the management of T2DM in adults along with diet and exercise. Teneligliptin is recently available in India and is also available in combination with other oral hypoglycemic agents at affordable prices. This review is aimed at exploring the status of teneligliptin with emphasis on its glycemic effects and non-glycemic clinical benefits associated with increasing GLP-1 & GIP.

scholarly journals Hypoglycemic Coma in a Hemodialysis Patient Receiving Blood Glucose-Lowering Therapy With the Single Agent Teneligliptin

2018 ◽  
Vol 11 ◽  
pp. 117954761876335 ◽  
Author(s):  
Takumi Minezumi ◽  
Shin-ichi Takeda ◽  
Yusuke Igarashi ◽  
Kentaro Sato ◽  
Yoshiaki Murakami ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Single Agent ◽  
Severe Hypoglycemia ◽  
Dipeptidyl Peptidase ◽  
Hypoglycemic Agents ◽  
Tolerability Profile ◽  
Oral Hypoglycemic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Hypoglycemic Coma ◽  
Dipeptidyl Peptidase 4 Inhibitors

Blood glucose management in patients undergoing dialysis is clinically challenging. In this population, most conventional oral hypoglycemic agents are contraindicated, especially from the perspective of pharmacokinetics. Dipeptidyl peptidase-4 inhibitors exert unique pharmacologic actions via glucose-dependent mechanism and have an excellent tolerability profile with a very low risk of hypoglycemia. Furthermore, the literature reports that some dipeptidyl peptidase-4 inhibitors such as teneligliptin can be administered at the usual dose, regardless of a patient’s level of renal impairment. In this article, we report a case of hypoglycemic coma with a blood glucose level of 23 mg/dL. The patient became fully conscious shortly after receiving a glucose injection; however, severe hypoglycemia recurred for approximately 1.5 days. It eventually disappeared on the discontinuation of teneligliptin, which was the only antidiabetic agent that he had received. The present case may provide deep insights into promoting the safe use of hypoglycemic agents in patients undergoing dialysis.

scholarly journals Degradation of Incretins and Modulation of Blood Glucose Levels by Periodontopathic Bacterial Dipeptidyl Peptidase 4

2017 ◽  
Vol 85 (9) ◽  
Author(s):  
Yuko Ohara-Nemoto ◽  
Manami Nakasato ◽  
Yu Shimoyama ◽  
Tomomi T. Baba ◽  
Takeshi Kobayakawa ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Dipeptidyl Peptidase ◽  
Oral Glucose ◽  
Content Type ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Flight Mass Spectrometry ◽  
Blood Glucose Levels ◽  
Molecular Events

ABSTRACT Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels. Cell-associated DPP4 activity was found in those microorganisms, which was effectively suppressed by inhibitors of human DPP4, and molecules sized 73 kDa in P. gingivalis, and 71 kDa in T. forsythia and P. intermedia were immunologically detected. The k cat/Km values of recombinant DPP4s ranged from 721 ± 55 to 1,283 ± 23 μM−1s−1 toward Gly-Pro-4-methylcoumaryl-7-amide (MCA), while those were much lower for His-Ala-MCA. Matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) analysis showed His/Tyr-Ala dipeptide release from the N termini of incretins, glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide, respectively, with the action of microbial DPP4. Moreover, intravenous injection of DPP4 into mice decreased plasma active GLP-1 and insulin levels, accompanied by a substantial elevation in blood glucose over the control after oral glucose administration. These results are the first to show that periodontopathic bacterial DPP4 is capable of modulating blood glucose levels the same as mammalian DPP4; thus, the incidence of periodontopathic bacteremia may exacerbate diabetes mellitus via molecular events of bacterial DPP4 activities.

scholarly journals A Male with Extreme Subcutaneous Insulin Resistance: A Case Report

2016 ◽  
Vol 23 (2) ◽  
pp. 209-213 ◽  
Author(s):  
Zuhayer Ahmed ◽  
Indrajit Prasad ◽  
Hafizur Rahman ◽  
Jalil Ansari ◽  
Khaled Hassan
Keyword(s):  
Insulin Resistance ◽  
Blood Glucose ◽  
Underdeveloped Country ◽  
Hypoglycemic Agents ◽  
High Dose ◽  
Subcutaneous Insulin ◽  
Oral Hypoglycemic Agents ◽  
Glucose Levels ◽  
Medical Issues ◽  
Insulin Autoantibody

AbstractIntroduction: Though insulin has no upper limit in dosage, we do not encounter very high dose requirements too often. The reported case is the first in Bangladesh to require more than 1000 international units (IU) of subcutaneous insulin per day.Case presentation: A 44-year old male diabetic patient from Bangladesh presented with unusually uncontrolled diabetes mellitus due to extreme insulin resistance. Despite dramatic increase in insulin step by step up to 1110 IU of concomitant short and intermediate acting insulin per day by subcutaneous route, his blood glucose remained over 12 mmol/L persistently, in all the fasting, pre-prandial, postprandial and random samples. He was also treated with several oral hypoglycemic agents including metformin, vildagliptin, glimepiride, pioglitazone and miglitol along with insulin but blood glucose levels remained almost unchanged. However, intravenous infusion of insulin over 4 hours caused a plummet in the glucose level. His blood test for insulin autoantibody was negative.Conclusion: This paper provides a scope to review literatures on extreme subcutaneous insulin resistance and its management. It also reveals the limitations of management due to lack of facilities in an underdeveloped country, which hinders proper exploration to many medical issues.

scholarly journals COMPARATIVE STUDY OF ORAL HYPOGLYCEMIC AGENTS IN TYPE-2 DIABETES OBESE PATIENTS

2018 ◽  
Vol 11 (6) ◽  
pp. 505
Author(s):  
Venkateswarlu Konuru ◽  
Ram Mohan Reedy T
Keyword(s):  
Blood Sugar ◽  
Adverse Drug Reactions ◽  
Glycosylated Hemoglobin ◽  
Dipeptidyl Peptidase ◽  
Hypoglycemic Agents ◽  
Diabetic Patients ◽  
Drug Reactions ◽  
Oral Hypoglycemic Agents ◽  
Peptidase Inhibitors

  Objectives: The aim of this study was to evaluate safety and efficacy of oral hypoglycemic agents in obese Type-2 diabetic patients. The objectives are to compare fasting and postprandial blood sugar (PPBS) levels, to compare body mass index (BMI) in all the groups, and to identify glycosylated hemoglobin levels and adverse drug reactions (if present) in all the groups.Method: This is a prospective observational study conducted in care diabetic center over a period of 1 year. All the patients those are receiving only oral hypoglycemic agents continuously over a period of 3 months and BMI ≥30 were enrolled. The patients receiving insulin were excluded. Patients were followed over a period of 3 months and were reviewed on visit basis (every 30 days). All the necessary information was collected into the data collection form that includes demographic details (age, gender, etc.), past medication history, current treatment charts, and their relevant laboratory reports (fasting blood sugar levels [mg/dl], PPBS levels [mg/dl], glycosylated hemoglobin A1c [HbA1c] (%), and BMI [kg/m2]).  Results: A total of 395 patients were recruited into the study and the drugs received by the population were found to be metformin+sulfonylureas (33%), metformin+pioglitazone (26%), and metformin+dipeptidyl peptidase inhibitors (DPI) (23%). A significant reduction in HbA1c was seen in all groups of patients. Adverse drug reactions observed were hypoglycemia, pedal edema, and itching distributed to drugs metformin+DPI, respectively. A significant reduction in BMI was seen in patients receiving DPI and BMI was found to be increased in other groups of patients.Conclusion: Overall, three classes of drugs were found to have similar efficacy. Sulfonylureas were commonly associated with hypoglycemia when compared to other drugs and weight reduction observed in dipeptidyl peptidase inhibitors.

scholarly journals Evaluation of Hypoglycaemic Effects of Dipeptidyl Peptidase–4 Inhibitors and Biguanide on Type-2 Diabetic subjects: A six months trial

2020 ◽  
Vol 24 (4) ◽  
pp. 368-373
Author(s):  
Naghma Ms. ◽  
Sadia M Azam Khan ◽  
Atta Ullah Khan ◽  
Zahoor Ahmed ◽  
Muhammad Umar ◽  
...  
Keyword(s):  
Venous Blood ◽  
Hypoglycemic Agents ◽  
Dietary Control ◽  
Oral Hypoglycemic Agents ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Group A ◽  
Group B ◽  
Type 2 Diabetic

Objective: This trial was conducted to evaluate the effectiveness of oral hypoglycemic agents on diabetic control and biochemical parameters of known diabetic subjects. Introduction:  T2DM   occurs due to abnormal metabolism of carbohydrate, proteins and lipids leading to increased blood glucose characterized by polyuria and polydypsia due to relative 5deficiency or lack of insulin. Beside dietary control and insulin therapy, various oral hypoglycemic such as sulfonylurea biguanide, thiazolidinedione, DPP–4 inhibitors, glucagon–like peptide inhibitors and SGL2.   Material and Methods: This comparative trial was carried out on previously diagnosed type–2 diabetic subjects. This trial was conducted at health care centers of District Nowshehra viz. NMC Nowshehra, DHQ Hospital Nowshehra, and ICS, Peshawar in collaboration with KMC and PIMC Peshawar, Khyber Pakhtunkhwa, Pakistan. A total of 200 known diabetic subjects were randomly recruited on the basis of predetermined selection criteria and were splited into two groups. Group A having 100 diabetic subjects was given DPP–4 inhibitor; Sitagliptin 50 mg two times a day alone for six (06) months while Group B comprising of 100 patients were treated   with combination of DPP–4 inhibitor (Sitagliptin 50 mg 1BD) and Metformin in a dose of 500 mg two times a day. Venous blood samples were taken from each patient in both fasting (10–12 hour night long fast) and random (2 hour post prandial) state. FBS, RBS, HbA1C, S. creatinine and fasting S. lipid profile were determined by using spectrophotometric colorimetric methods using kits (procured from Elitech, Spain) at  03 and 06 months follow up. Inclusion criteria was subjects with T2DM of age 18 years and above. T2DM patients on insulin, diabetic nephropathy and retinopathy were excluded. The data was analyzed by using SPSS software version 20. Results: Significant results (p < 0.05) were seen for glycemic control (FBS, RBS, HbA1C) in Group B as compare to Group A patients.

scholarly journals Additive inhibitory effect of the peels of Citrus limon and Citrus sinensis against amylase and glucosidase activity

2020 ◽  
Vol 11 (4) ◽  
pp. 6876-6880
Author(s):  
Rangarajan N ◽  
Sangeetha R ◽  
Mohanasundaram S ◽  
Sampath V ◽  
Porkodi K ◽  
...  
Keyword(s):  
Orange Peel ◽  
Inhibitory Effect ◽  
The Body ◽  
Hypoglycemic Agents ◽  
Citrus Limon ◽  
Oral Hypoglycemic Agents ◽  
Major Health Problem ◽  
Glucose Levels ◽  
Inhibitory Potential ◽  
The Individual

Diabetes mellitus is a major health problem and it is a metabolic disorder characterized by hyperglycemia. Decreased utilization of glucose by the body cells and continuous raise in the plasma glucose levels are the major characteristic symptoms of diabetes. Uncontrolled hyperglycemia is associated with pathological conditions, mostly micro and macrovascular. Treatment for diabetes is aimed at the management of hyperglycemia using oral hypoglycemic agents which inhibit carbohydrate degrading enzymes, namely amylase and glucosidase. The purpose of this study was to investigate the naturally available inhibitors of amylase and glucosidase present in the peels of citrus fruits such as lemon and orange. The hydroalcoholic extract of the fruit peels were studied for their amylase and glucosidase inhibitory potential and the extract of lemon peel was found to exhibit better inhibition than the orange peel. The extracts were further evaluated for their additive effect. The combined effect of the extracts (50% inhibition achieved at 40 and 80mcg) proved to exhibit better inhibitory potential than the individual effect (50% inhibition achieved at 80 and 160mcg). Thus, from this study, it was very clear that our choice drug sources is containing potential antidiabetic principles that need to be studied further to understand the mechanism of action in detail.

scholarly journals Diabetes Mellitus and Colon Carcinogenesis: Expectation for Inhibition of Colon Carcinogenesis by Oral Hypoglycemic Drugs

2019 ◽  
Vol 1 (2) ◽  
pp. 273-289 ◽  
Author(s):  
Junichi Kato ◽  
Yohei Shirakami ◽  
Masahito Shimizu
Keyword(s):  
Diabetes Mellitus ◽  
Colorectal Cancer ◽  
Colon Carcinogenesis ◽  
Basic Research ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Antitumor Effects ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Oral Hypoglycemic Drugs

The global deaths due to colorectal cancer and diabetes mellitus have increased by 57% and 90%, respectively. The relationship between various cancers and diabetes mellitus has been shown in multiple epidemiological studies. Hence, better management of diabetes mellitus is expected to reduce the risk of various cancers. This review focuses on colorectal cancer and aims to summarize recent findings on the antitumor effects of various oral hypoglycemic drugs on colorectal cancer and their estimated mechanisms. Of the seven classes of oral hypoglycemic agents, only metformin was found to have suppressive effects on colorectal cancer in both clinical and basic research. Clinical and basic researches on suppressing effects of glinides, dipeptidyl peptidase-4 inhibitors, thiazolidinedione, α-glucosidase inhibitors, and sodium glucose cotransporter-2 inhibitors against colon carcinogenesis have been insufficient and have not arrived at any conclusion. Therefore, further research regarding these agents is warranted. In addition, the suppressive effects of these agents in healthy subjects without diabetes should also be investigated.

scholarly journals New Molecular Insights into the Inhibition of Dipeptidyl Peptidase-4 by Natural Cyclic Peptide Oxytocin

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3887
Author(s):  
Veera C. S. R. Chittepu ◽  
Poonam Kalhotra ◽  
Tzayhri Osorio-Gallardo ◽  
Cristian Jiménez-Martínez ◽  
Raúl René Robles-de la Torre ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Serine Protease ◽  
Cyclic Peptides ◽  
Cyclic Peptide ◽  
Dipeptidyl Peptidase ◽  
Dependent Manner ◽  
Protease Inhibition ◽  
Dipeptidyl Peptidase 4 ◽  
Glucose Levels ◽  
Dpp4 Inhibition

Protease inhibition has led to treating many diseases and has been successful in producing many commercial drugs by pharmaceutical companies. Among many proteases, serine protease has been attractive in treating metabolic disorder diabetes mellitus (DM). Gliptins have been proven to inhibit dipeptidyl peptidase-4 (DPP4), a serine protease, and are an emerging therapeutic drug target to reduce blood glucose levels, but until now there is no natural cyclic peptide proven to inhibit serine protease DPP4. This study demonstrates the potential mechanism of natural cyclic peptide oxytocin (OXT) as a DPP4 inhibitor. To achieve this, initially, activity atlas and field-based models of DPP4 inhibitors were utilized to predict the possible features of positive and negative electrostatic, hydrophobic, and activity shapes of DPP4 inhibition. Oxytocin binding mode, flexibility, and interacting residues were studied using molecular docking simulations studies. 3D-RISM calculations studies revealed that the stability of water molecules at the binding site are favorable. Finally, an experimental study using fluorescence assay revealed OXT inhibits DPP4 in a concentration-dependent manner in a significant way (p < 0.05) and possess IC50 of 110.7 nM. These new findings significantly expand the pharmaceutical application of cyclic peptides, and in specific OXT, and implicate further optimization of OXT inhibition capacity to understand the effect of DPP4 inhibition. This work highlights the development of natural cyclic peptides as future therapeutic peptides to reduce glucose levels and treat diabetes mellitus.

An Overview on Anti Diabetic Drugs and Development

2016 ◽  
Vol 4 (2) ◽  
pp. 113-123 ◽  
Author(s):  
Ved Prakash Singh ◽  
Keyword(s):  
Diabetes Mellitus ◽  
The United States ◽  
Insulin Analogues ◽  
Hypoglycemic Agents ◽  
Oral Hypoglycemic Agents ◽  
Related Complication ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Target Organs ◽  
Treatment Of Diabetes

Diabetes mellitus is one of the world’s major diseases and is the third leading cause of death in the United States after heart disease and cancer. In the India, about 2–6% population suffer from diabetes or related complication. Anti-diabetic drugs treat diabetes mellitus by lowering glucose levels in the blood. Mostly anti-diabetic drugs are administered orally except the insulin, exenatide, and pramlintide. There are different types of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, and many other factors. Treatments include the agents which increase the amount of insulin secreted by the pancreas, or increase the sensitivity of target organs to insulin, and agents which decrease the rate at which glucose is absorbed from the gastrointestinal tract. People are mainly focused on insulin, insulin analogues, oral hypoglycemic agents and various other complementary and alternate medicines to control the blood glucose levels in diabetes. The present review summarizes in brief about the drugs used for treatment of diabetes mellitus.

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