scholarly journals Influence of novel GPR119 agonist in combination with metformin and sitagliptin on glycemia, body weight and food intake in rats fed a high-fat diet

2019 ◽  
Vol 16 (3) ◽  
pp. 46-54
Author(s):  
Ivan N. Tyurenkov ◽  
Denis V. Kurkin ◽  
Dmitry A. Bakulin ◽  
Elena V. Volotova ◽  
Ekaterina O. Logvinova ◽  
...  

BACKGROUND: Metabolic syndrome and obesity are often precursors of type 2 diabetes mellitus (DM), and current recommendations indicate the advisability of early initiation of drug therapy at the stage of prediabetes. Drugs with incretin activity are one of the priority groups for monotherapy of type 2 diabetes in the onset of the disease, and certain drugs are used to treat obesity. GPR119 agonists increase the secretion of endogenous incretins, and their effectiveness in the treatment of type 2 diabetes and obesity in mono- and combination therapy is currently being actively studied. AIM. To evaluate of the effect of administration of a GPR119 receptor agonist, its combination with metformin or sitagliptin on body weight, food intake and glycemia in rats under a high-calorie diet. MATERIALS AND METHODS: The study was conducted on 56 outbred female rats aged 78 months and an initial weight of 305320 g. Compound ZB-16 is a highly active GPR119 receptor agonist (EC50 = 7 nM). For 12 weeks, the animals were kept on a high-fat and carbohydrate diet and at the same time received the compound ZB-16, metformin and sitagliptin, or its combination (ZB-16 + metformin and ZB-16 + sitagliptin). During the experiment, the weight of the animals, the mass of feed eaten, as well as the level of glycemia after 6 hours of fasting and with an oral glucose load were assessed. RESULTS: In animals of the control group that were on a high-calorie and fatty diet for 12 weeks, an increase in body weight, glycemia and a decrease in the rate of glucose utilization were observed. The introduction of the GPR119 agonist (ZB-16) for 12 weeks led to a significant reduction in the amount of food consumed, limited weight gain and prevented the development of carbohydrate metabolism disorders. The addition of sitagliptin and especially metformin to therapy with the GPR119 agonist significantly increased the effectiveness of therapy compared to the control group, which was expressed in the normalization of animal body weight and glycemia (p 0.05). CONCLUSIONS: The introduction of a combination of the GPR119 agonist (compound ZB-16) with metformin and sitagliptin is more effective than monotherapy in terms of weight gain, food intake, and also prevents the development of carbohydrate metabolism disorders in animals when kept on a high-fat and carbohydrate diet.

Author(s):  
ASHUTOSH KUMAR YADAV ◽  
REETU ◽  
ARUN GARG

Objective: India is the “diabetes capital of the world” with 62.4 million Indians having type 2 diabetes in 2011. A major risk factor for insulin resistance is obesity, which is generally caused by regular physical inactivity and high-fat diet (HFD). Obesity and diabetes are closely related to each other as about 80% of diabetics are obese. Obesity is a common finding in type 2 diabetes. The objective of the study was to investigate the antidiabetic effects of [10]-gingerol in streptozotocin (STZ)- and HFD-induced diabetic rats. Methods: Wistar rats were used for the study. Animals were divided into six groups. The six groups in this study were, Group I (normal control), Group II (diabetic control), Group III (glibenclamide at 5 mg/kg p.o.), Group IV (orlistat at 60 mg/kg p.o.), Group V ([10]-gingerol at 15 mg/kg p.o.), and Group VI [10]-gingerol (30 mg/kg p.o.), respectively. The antidiabetic activity was assessed using blood glucose level, body weight, and various biochemical parameters such as serum total cholesterol (TC) level, triglyceride (TG) level, high-density lipoproteins (HDLs), total protein (TP), serum alanine transaminase, and aspartate aminotransferase (serum glutamic-oxaloacetic transaminase), respectively. Results: [10]-gingerol exhibited an antidiabetic effect by significantly decreased the level of blood glucose, body weight, TC, TG, TP, and increase HDL. The results of the study demonstrated that the treatment with [10]-gingerol significantly (p<0.05) and dose dependently prevented STZ- and HFD-induced diabetic rats. Conclusions: The findings of the study suggest that [10]-gingerol possesses potential antidiabetic activity as it lowers serum glucose level.


2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Yu Zhou

Objective The clinical manifestations of diabetic cognitive dysfunction are decreased visual spatial ability, executive dysfunction, mental activity speed and attention, and decreased abstract logical reasoning. Cognitive dysfunction is irreversible. Timely and accurate assessment and diagnosis, early detection and intervention to delay disease progression are particularly critical. The Cognitive Assessment Scale plays an important role in screening for cognitive dysfunction in diabetes. To observe the effects of motor functional therapy on cognitive impairment and blood glucose, blood lipids, body weight, body composition, and maximal oxygen uptake in patients with type 2 diabetes. Methods A total of 63 elderly patients with type 2 diabetes mellitus in Chengdu community aged ≥65 years and educated for ≥12 years were enrolled in the motor function therapy group according to the simple mental state examination (MMSE) score (diabetes cognitive impairment, MMSE total score) ≥ 20 points, aerobic exercise group, n = 21) and functional function therapy group (diabetes cognitive impairment, MMSE total score ≥ 20 points, resistance exercise group, n = 21). The adult community of diabetes in Chengdu (normal cognitive function) with age ≥ 65 years, education time ≥ 12 years, and MMSE total score ≥ 24 points was used as the control group (n=21). Montreal Cognitive Assessment Scale (MOCA): MOCA is an assessment tool developed by Nasreddine and clinically proven to be used for rapid screening of MCI. There were no statistical differences in baseline data (age, gender, and hypertension incidence) among the 3 groups of patients. The LOTCA scale was used to evaluate the cognitive function of the subjects and to compare between groups. Sixty-three patients with type 2 diabetes were randomly divided into aerobic exercise intensity group (50% VO2max) (n=21), resistance exercise intensity group and control group (n=21). Both the aerobic exercise group and the resistance exercise group underwent a 12-week moderate-intensity exercise three times a week. The resistance middle strength group was trained 2 groups each time, each group was 25 minutes, the group rested for 5 minutes, 55 minutes in total, and the aerobic medium intensity group continued to exercise for 55 minutes. All patients underwent fasting blood glucose (FPG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), body weight, and fat weight (FW) before and after training. , lean body mass (LBM), maximal oxygen uptake (VO2max) determination; measure the energy expenditure of word movement and the total energy expenditure of the entire exercise process. Results There were no significant differences among the three groups before the test (P>0.05). All the indexes of the medium-intensity resistance exercise group and the medium-intensity aerobic exercise group were significantly different from the control group (P<0.05). After the MOCA score test There was an improvement in the score before the trial, and the total score of LOTCA was significantly different among the three groups. In addition to perceptual sub-items (item identification), the aerobic exercise group and the resistance exercise group LOTCA scale in perceptual sub-projects (incomplete object recognition), visual motion organization and its sub-projects (copying two-dimensional graphics, building blocks) The design and puzzle) project scores were higher than before the test, close to the control group score. The scores of the two groups of exercise therapy in the thinking operation and its sub-projects (Riska organized shape classification, picture arrangement B and geometric reasoning) and attention-focused items were lower than the control group. Compared with the resistance exercise, there was a significant difference in the maximum oxygen uptake between aerobic exercise and resistance exercise (P<0.05). Compared with the total exercise energy consumption in the first 6 weeks, the aerobic exercise group was superior to the resistance exercise group. The total exercise energy expenditure was compared in the last 6 weeks, and the resistance exercise group was superior to the aerobic exercise group. Conclusions Elderly patients with type 2 diabetes may have cognitive impairment earlier. In the absence of differences in exercise, the aerobic exercise group and the resistance exercise group improve cognitive impairment, blood sugar, blood fat, body weight, and body composition in patients with type 2 diabetes. There is no significant difference. Compared with MMSE, LOTCA has the advantage of identifying early cognitive impairment in elderly patients with type 2 diabetes and distinguishing the severity of the damage.  


Author(s):  
Sarita Mulkalwar ◽  
Tanya Gupta ◽  
Vishwanath Kulkarni ◽  
A. V. Tilak ◽  
B. T. Rane ◽  
...  

Background: As of 2018, 2.1 billion people nearly 30% of the world’s population are either obese or overweight. Worldwide obesity has nearly tripled since 1975. It is an emerging health problem with major adverse effects on health. It is a risk factor for many chronic diseases but is best known for its role in metabolic syndrome, which can lead to type 2 diabetes mellitus as well as cardiovascular diseases. Anti-obesity drugs are available but have many side effects. Voglibose, an antidiabetic drug, is an alpha glucosidase inhibitor which shows promising results in the reduction of body weight with minimal side effects.Methods: Voglibose (7 mg/kg) was administered to rats fed with normal laboratory chows and high fat diet to see its effect on body weight, body mass index, abdominal and thoracic circumference, and lipid profile at the end of 12 weeks.Results: Administration of voglibose significantly reduced food consumption, feed efficiency and increase in body weight induced by high fat diet in rats. Rats fed on normal diet also showed reductions in the same parameters, suggesting its weight lowering effect. Reductions in the anthropometric measurements, hypolipidemic effects and glucose lowering effects were also observed.Conclusions: Voglibose prevented high fat diet-induced obesity and improvement in metabolic profile, which ultimately has systemic effects on body weight in rats. Further studies are needed to see its potential therapeutic use in obese patients with type 2 diabetes mellitus, and related complications.


2019 ◽  
Vol 12 ◽  
pp. 117955141882504
Author(s):  
Naohiko Ueno

Objective: Mexiletine is an anti-arrhythmic agent also used for the treatment of painful diabetic neuropathy. In this study, the effect of mexiletine on body weight was evaluated in type 2 diabetes patients with diabetic neuropathy exhibiting visceral obesity. Methods: Type 2 diabetes patients with neuropathy exhibiting visceral obesity (n = 21) treated by mexiletine (300 mg/day) and a control group of type 2 diabetes patients with the same condition who received vitamin B12 (n = 12) were retrospectively evaluated. Body weight, waist circumference, hemoglobin A1c (HbA1c), blood pressure, liver function, serum lipids, and serum uric acid were assessed before and 6 months after the treatment. Results: Mexiletine significantly decreased body weight and waist circumference. The changes in body weight and waist circumference in 6 months in the mexiletine group were greater than in the control group. In metabolic parameters, there were significant decreases in triglyceride (TG) and serum uric acid. There were positive relationships between the change in body weight and the changes in TG, uric acid, alanine aminotransferase (ALT), and HbA1c. Conclusions: Mexiletine may affect body weight regulation. It ameliorated the metabolic parameters possibly by decreasing visceral fat. Further study should be performed to clarify the mechanism of the effect.


2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Chuang Yuan ◽  
Christopher W. K. Lai ◽  
Lawrence W. C. Chan ◽  
Meyrick Chow ◽  
Helen K. W. Law ◽  
...  

Aims.To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes.Methods.76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group(n=36)and control group(n=40). The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention.Results.There was a significant reduction in hemoglobin A1c (HbA1c,-0.2±0.56% versus0.08±0.741%;P<0.05) and body weight (-1.19±1.39 kg versus-0.61±2.04 kg;P<0.05) in the intervention group as compared to the control group. However, no significant improvements were found in other metabolic markers, CIMT and CAS(P>0.05).Conclusions.DSME can improve HbA1c and body weight in patients with type 2 diabetes.


2014 ◽  
Vol 307 (8) ◽  
pp. E712-E719 ◽  
Author(s):  
Takeru Sakai ◽  
Toru Kusakabe ◽  
Ken Ebihara ◽  
Daisuke Aotani ◽  
Sachiko Yamamoto-Kataoka ◽  
...  

Leptin may reduce pancreatic lipid deposition, which increases with progression of obesity and can impair β-cell function. The insulinotropic effect of glucagon-like peptide-1 (GLP-1) and the efficacy of GLP-1 receptor agonist are reduced associated with impaired β-cell function. In this study, we examined whether leptin could restore the efficacy of exenatide, a GLP-1 receptor agonist, in type 2 diabetes with increased adiposity. We chronically administered leptin (500 μg·kg−1·day−1) and/or exenatide (20 μg·kg−1·day−1) for 2 wk in a mouse model of type 2 diabetes with increased adiposity induced by streptozotocin and high-fat diet (STZ/HFD mice). The STZ/HFD mice exhibited hyperglycemia, overweight, increased pancreatic triglyceride level, and reduced glucose-stimulated insulin secretion (GSIS); moreover, the insulinotropic effect of exenatide was reduced. However, leptin significantly reduced pancreatic triglyceride level, and adding leptin to exenatide (LEP/EX) remarkably enhanced GSIS. These results suggested that the leptin treatment restored the insulinotropic effect of exenatide in the mice. In addition, LEP/EX reduced food intake, body weight, and triglyceride levels in the skeletal muscle and liver, and corrected hyperglycemia to a greater extent than either monotherapy. The pair-feeding experiment indicated that the marked reduction of pancreatic triglyceride level and enhancement of GSIS by LEP/EX occurred via mechanisms other than calorie restriction. These results suggest that leptin treatment may restore the insulinotropic effect of exenatide associated with the reduction of pancreatic lipid deposition in type 2 diabetes with increased adiposity. Combination therapy with leptin and exenatide could be an effective treatment for patients with type 2 diabetes with increased adiposity.


2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Eun Young Park ◽  
Eung Hwi Kim ◽  
Mi Hwi Kim ◽  
Young Wan Seo ◽  
Jung Im Lee ◽  
...  

Ecklonia cava (E. cava)is a brown alga that has beneficial effects in models of type 1 and type 2 diabetes. However, the effects ofE. cavaextracts on diet-induced obesity and type 2 diabetes have not been specifically examined. We investigated the effects ofE. cavaon body weight, fat content, and hyperglycemia in high-fat diet- (HFD) induced obese mice and sought the mechanisms involved. C57BL/6 male mice were fed a HFD (60% fat) diet or normal chow. After 3 weeks, the HFD diet group was given extracts (200 mg/kg) ofE. cavaharvested from Jeju (CA) or Gijang (G-CA), Korea or PBS by oral intubation for 8 weeks. Body weights were measured weekly. Blood glucose and glucose tolerance were measured at 7 weeks, and fat pad content and mRNA expression of adipogenic genes and inflammatory cytokines were measured after 8 weeks of treatment. G-CA was effective in reducing body weight gain, body fat, and hyperglycemia and improving glucose tolerance as compared with PBS-HFD mice. The mRNA expression of adipogenic genes was increased, and mRNA expression of inflammatory cytokines and macrophage marker gene was decreased in G-CA-treated obese mice. We suggest that G-CA reduces obesity and glucose levels by anti-inflammatory actions and improvement of lipid metabolism.


2010 ◽  
Vol 104 (11) ◽  
pp. 1628-1634 ◽  
Author(s):  
Bethany P. Cummings ◽  
Kimber L. Stanhope ◽  
James L. Graham ◽  
Steven C. Griffen ◽  
Peter J. Havel

EPA or fish oil supplementation has been suggested as treatments for the prevention of type 2 diabetes mellitus (T2DM) due to their lipid-lowering and potential insulin-sensitising effects. We investigated the effects of supplementation with EPA (1 g/kg body weight per d) or fish oil (3 g/kg body weight per d) on the age of onset of T2DM and circulating glucose, insulin, lipids, leptin and adiponectin in UC Davis (UCD)-T2DM rats. Animals were divided into three groups starting at 1 month of age: control, EPA and fish oil. All the animals were followed until diabetes onset or for up to 12 months of age. Monthly fasting blood samples were collected for the measurement of glucose, lipids, hormones and C-reactive protein (CRP). Neither EPA nor fish oil delayed the onset of T2DM or altered fasting plasma glucose, insulin, CRP, adiponectin or leptin concentrations. The groups did not differ in energy intake or body weight. Fish oil treatment lowered fasting plasma TAG concentrations by 39 (sd 7) % (P < 0·001) and EPA lowered fasting plasma NEFA concentrations by 23 (sd 5) % (P < 0·05) at 4 months of age compared with the control group. EPA and fish oil lowered fasting plasma cholesterol concentrations at 4 months of age by 19 (sd 4) and 22 (sd 4) % compared with the control group, respectively (both P < 0·01). In conclusion, EPA and fish oil supplementation lowers circulating lipid concentrations, but does not delay the onset of T2DM in UCD-T2DM rats.


2019 ◽  
Vol 181 (6) ◽  
pp. R211-R234 ◽  
Author(s):  
Michael A Nauck ◽  
Juris J Meier

GLP-1, a peptide hormone secreted from the gut, stimulating insulin and suppressing glucagon secretion was identified as a parent compound for novel treatments of diabetes, but was degraded (dipeptidyl peptidase-4) and eliminated (mainly by kidneys) too fast (half-life 1–2 min) to be useful as a therapeutic agent. GLP-1 receptor agonist has been used to treat patients with type 2 diabetes since 2007, when exenatide (twice daily) was approved in 2007. Compounds with longer duration of action (once daily, once weekly) and with increasingly better efficacy with respect to glycaemic control and body weight reduction have been developed, and in a recent ADA/EASD consensus statement, were recommended as the first injectable diabetes therapy after failure of oral glucose-lowering medications. Most GLP-1 receptor agonists (lixisenatide q.d., liraglutide q.d., exenatide q.w., dulaglutide q.w., albiglutide q.w., semaglutide q.w., all for s.c. injection, and the first oral preparation, oral semaglutide) have been examined in cardiovascular outcomes studies. Beyond proving their safety in vulnerable patients, most of whom had pre-existing heart disease, liraglutide, semaglutide, albiglutide, and dulaglutide reduced the time to first major adverse cardiovascular events (non-fatal myocardial infarction and stroke, cardiovascular death). Liraglutide, in addition, reduced cardiovascular and all-cause mortality. It is the purpose of the present review to describe clinically important differences, regarding pharmacokinetic behaviour, glucose-lowering potency, effectiveness of reducing body weight and controlling other cardiovascular risk factors, and of the influence of GLP-1 receptor agonist treatment on cardiovascular outcomes in patients either presenting with or without pre-existing cardiovascular disease (atherosclerotic, ischemic or congestive heart failure).


Author(s):  
Martin Fonkoua ◽  
W. Tazon Arnold ◽  
R. Françoise Ntentié ◽  
B. Azantsa Kingue ◽  
G. Takuissu Nguemto ◽  
...  

Aim:  DNA methylation profile is involved in several physiological processes. Its alterations in the liver of diabetic patients characterized by global hypomethylation are associated with the pathophysiology of type 2 diabetes and its complications. The present study has evaluated the effect of the aqueous extract of Alstonia boonei barks on the global methylation of hepatic DNA in association with hyperglycemia and diabetes complications induced by high-fat diet (HFD) feeding and administering of streptozotocin (STZ) which mimics the metabolic abnormalities very similar to those seen in human Type 2 diabetes. Methods: A. boonei barks were harvested, processed, dried, ground and an aqueous extraction was prepared (ratio 1/10 w/v). An in vivo study was conducted in an animal model of high-fat-streptozotocin (HF-STZ) induced diabetes. Rats were divided into five groups of five rats each: a normoglycemic group, an untreated hyperglycemic group, three hyperglycemic groups including two test groups receiving aqueous extract of A. boonei barks (AEAB) by esophageal gavage at the doses of 200 and 400 mg/kg body weight once daily and a reference group receiving metformin at 10 mg/kg body weight. After 28 days of experimentation during which fasting blood glucose levels were taken every 14 days under fasting conditions, the animals were sacrificed. Plasma and liver homogenate samples from the sacrificed rats were used for biochemical assays (markers of oxidative stress such as malondialdehyde level, superoxide dismutase (SOD) and catalase activity, and markers of lipid profile such as total cholesterol, and triglycerides, HDL-c, LDL-c and VLDL-c).  The analysis of the global DNA methylation profile was performed by the immunoprecipitation. Pearson's correlation was used to evaluate the relationship between the values. Results: The aqueous extract increased the hepatic DNA methylation by 0.41% and 0.63% at 200 and 400 mg/kg body weight, respectively, compared to metformin (0.47%±0, 05). This effect was significantly associated with the hypoglycemic effect obtained at 400 mg/kg body weight with a decrease in initial blood glucose level of -29.87%. Conclusion: AEAB reduces chronic hyperglycemia and prevents its complications by increasing global hepatic DNA methylation.


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