Effects of the SGLT2 inhibitor ipragliflozin on food intake, appetite-regulating hormones, and arteriovenous differences in postprandial glucose levels in type 2 diabetic rats

2018 ◽  
Vol 105 ◽  
pp. 1033-1041 ◽  
Author(s):  
Atsuo Tahara ◽  
Yoshinori Kondo ◽  
Toshiyuki Takasu ◽  
Hiroshi Tomiyama
Author(s):  
Eric Martial Deutchoua Ngounou ◽  
Yannick Dimitry Mang ◽  
Faustin Dongmo ◽  
Oumar Waassili Ibrahim Malla ◽  
Sélestin Sokeng Dongmo ◽  
...  

Aim and objective: Clerodendrum thomsoniae leaves are used in Cameroon to manage diabetes and its related disorders. The study aimed at investigating the antidiabetic effect of the aqueous extract on diet and dexamethasone induced diabetic rats. Methods: Young mature leaves of C thomsoniae were dried, finely powdered and submitted to aqueous extraction. The dehydrated extract was tested in rats at 3 doses 312.5, 625 and 1250 mg/kg based on the local use of the plant. The effect of the extract on the fasting blood glucose in normoglycemic rats and MACAPOS 1 type diet induced diabetic rats, using respectively glibenclamide and metformin as positive control groups, were investigated. Results: AECT significantly reduced blood glucose levels in normoglycemic rats (p<0.05) two hours after administration, from 83±2 mg/dL to 57.39±1.7 mg/dL with the dose of 1250 mg/kg. given the highest reduction rate of 30.86%. In normoglycemic rats 30 minutes after oral glucose overload, the maximum reduction rate was observed with glibenclamide 5 mg / kg and calculated at 49.90% followed by 36.39%, for the extract at 1250 mg / kg. After 30 days of repeated oral administration, AECT produced a reduction on blood glucose levels (p<0.05) in type 2 diabetic rats. This reduction in blood sugar was much more expressed with the dose of 1250mg/kg (73.52±0.71 mg/dL) followed by metformin 38mg/kg (70.21±0.89 mg/dL) as the normal control with no significant difference (P < 0.05). Conclusion: These results show that the antidiabetic activity of AECT can be explained by insulin stimulating effect, also give support to the traditional use of this plant.                   Peer Review History: Received 11 May 2021; Revised 17 June; Accepted 27 June, Available online 15 July 2021 Academic Editor: Dr. Asia Selman Abdullah,  Al-Razi university, Department of Pharmacy, Yemen, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.  Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 6.5/10 Average Peer review marks at publication stage: 8.0/10 Reviewer(s) detail: Dr. Terhemen Festus Swem, Department of Veterinary Physiology and Biochemistry, College of Veterinary Medicine, Federal University of Agriculture, Makurdi, Benue State, Nigeria, [email protected] Taha A.I. El Bassossy, Medicinal and Aromatic Plants Department, Desert Research Center, Cairo, Egypt, [email protected] Prof. Dr. Ali Gamal Ahmed Al-kaf, Sana'a university, Yemen, [email protected]   Similar Articles: ANTIDIABETIC AND ANTIHYPERLIPIDEMIC ACTIVITY OF DRACAENA CINNABARI BALF. RESIN ETHANOLIC EXTRACT OF SOQATRA ISLAND IN EXPERIMENTAL ANIMALS THE SCOPING REVIEW OF CHINESE AND WESTERN MEDICINE TREATMENT OF DIABETIC FOOT IN ASIA ANTIHYPERGLYCEMIC AND ANTI-OXIDANT POTENTIAL OF ETHANOL EXTRACT OF VITEX THYRSIFLORA LEAVES ON DIABETIC RATS EFFECTS OF EMODIN ON BLOOD GLUCOSE AND BODY WEIGHT IN TYPE 1 DIABETIC RATS


2002 ◽  
Vol 29 (5-6) ◽  
pp. 423-427 ◽  
Author(s):  
Kiyoshi Ichikawa ◽  
Tokuhisa Yamato ◽  
Kazuma Ojima ◽  
Atsutoshi Tsuji ◽  
Kohtaro Ishikawa ◽  
...  

Biomedicines ◽  
2020 ◽  
Vol 8 (3) ◽  
pp. 43 ◽  
Author(s):  
Abdelaziz M. Hussein ◽  
Elsayed A. Eid ◽  
Medhat Taha ◽  
Rami M. Elshazli ◽  
Raouf Fekry Bedir ◽  
...  

The present study investigated the possible cardioprotective effects of GLP1 and SGLT2i against diabetic cardiomyopathy (DCM) in type 2 diabetic rats and the possible underlying mechanisms. Methods: Thirty-two male Sprague Dawley rats were randomly subdivided into 4 equal groups: (a) control group, (b) DM group, type 2 diabetic rats with saline daily for 4 weeks, (c) DM + GLP1, as DM group with GLP1 analogue (liraglutide) at a dose of 75 µg/kg for 4 weeks, and (d) DM + SGLT2i as DM group with SGLT2 inhibitor (dapagliflozin) at a dose of 1 mg/kg for 4 weeks. By the end of treatment (4 weeks), serum blood glucose, homeostasis model assessment insulin resistance (HOMA-IR), insulin, and cardiac enzymes (LDH, CK-MB) were measured. Also, the cardiac histopathology, myocardial oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and CAT) and norepinephrine (NE), myocardial fibrosis, the expression of caspase-3, TGF-β, TNF-α, and tyrosine hydroxylase (TH) in myocardial tissues were measured. Results: T2DM caused significant increase in serum glucose, HOMA-IR, serum CK-MB, and LDH (p < 0.05). Also, DM caused significant myocardial damage and fibrosis; elevation of myocardial MDA; NE with upregulation of myocardial caspase-3, TNF-α, TGF-β, and TH; and significant decrease in serum insulin and myocardial GSH and CAT (p < 0.05). Administration of either GLP1 analog or SGLT2i caused a significant improvement in all studied parameters (p < 0.05). Conclusion: We concluded that both GLP1 and SGLT2i exhibited cardioprotective effects against DCM in T2DM, with the upper hand for SGLT2i. This might be due to attenuation of fibrosis, oxidative stress, apoptosis (caspase-3), sympathetic nerve activity, and inflammatory cytokines (TNF-α and TGF-β).


2018 ◽  
Vol 52 (1) ◽  
pp. 6-16 ◽  
Author(s):  
Ayodele Olufemi Morakinyo ◽  
Titilola Aderonke Samuel ◽  
Daniel Abiodun Adekunbi

Abstract Objective. We investigated the effects of magnesium supplementation on glucose tolerance, insulin sensitivity, oxidative stress as well as the concentration of insulin receptor and glucose transporter-4 in streptozotocin-nicotinamide induced type-2 diabetic (T2D) rats. Methods. Rats were divided into four groups designated as: 1) control (CTR); 2) diabetic untreated (DU); 3) diabetic treated with 1 mg of Mg/kg diet (Mg1-D); and 4) diabetic treated with 2 mg of Mg/kg diet (Mg2-D). T2D was induced with a single intraperitoneal (i.p.) injection of freshly prepared streptozotocin (55 mg/kg) aft er an initial i.p. injection of nicotinamide (120 mg/kg). Glucose tolerance, insulin sensitivity, lipid profile, malondialdehyde (MAD) and glutathione content, insulin receptors (INSR) and glucose transporter-4 (GLUT4), fasting insulin and glucose levels were measured, and insulin resistance index was calculated using the homeostatic model assessment of insulin resistance (HOMA-IR). Results. Magnesium supplementation improved glucose tolerance and lowered blood glucose levels almost to the normal range. We also recorded a noticeable increase in insulin sensitivity in Mg-D groups when compared with DU rats. Lipid perturbations associated T2D were significantly attenuated by magnesium supplementation. Fasting glucose level was comparable to control values in the Mg-D groups while the HOMA-IR index was significantly lower compared with the DU rats. Magnesium reduced MDA but increased glutathione concentrations compared with DU group. Moreover, INSR and GLUT4 levels were elevated following magnesium supplementation in T2D rats. Conclusion. These findings demonstrate that magnesium may mediate effective metabolic control by stimulating the antioxidant defense, and increased levels of INSR and GLUT4 in diabetic rats.


Obesity Facts ◽  
2020 ◽  
pp. 1-11
Author(s):  
Ke Lu ◽  
Xiaoyan Chen ◽  
Xuelian Deng ◽  
Juan Long ◽  
Jianhua Yan

<b><i>Objective:</i></b> To investigate the relationship of central and peripheral ghrelin during an exendin-4 (Ex-4) intervention to feeding in obese type 2 diabetic rodents. <b><i>Methods:</i></b> Animal models of diet-induced obesity (DIO) and type 2 diabetes were developed using male Sprague-Dawley rats fed with a high-fat diet and induced into DIO-streptozotocin diabetic rats. Ex-4 or the glucagon-like peptide-1 (GLP-1) receptor agonist exendin fragment-[9-39] (Ex-9) was intracerebroventricularly (ICV) administered. Multivariate linear regression analysis was performed to investigate potential predictors of food intake after Ex-4 administration. <b><i>Results:</i></b> ICV administration of Ex-4 significantly inhibited feeding and decreased weight, plasma active ghrelin, hypothalamic ghrelin, and gastric ghrelin levels. The changes in hypothalamic ghrelin and plasma ghrelin could predict the amount of 8-h average food intake. Central preadministration of Ex-9 followed by treatment with Ex-4 could inhibit the decrease in feeding at 0.5, 2, and 8 h. It could also inhibit the decrease in hypothalamic ghrelin at 0.5, 2, and 8 h, as well as in plasma and gastric ghrelin at 2 and 8 h. <b><i>Conclusions:</i></b> In a GLP-1 receptor-dependent manner, central and peripheral ghrelin play a vital role in the inhibition of feeding by Ex-4 administration. Hypothalamic ghrelin, but not plasma ghrelin, may be involved in central Ex-4 inhibition of feeding in the very early feeding period.


2016 ◽  
Vol 57 (1) ◽  
pp. 13-21 ◽  
Author(s):  
Xun Cao ◽  
Xiao Zhou ◽  
Xiao-Min Liu ◽  
Li-Hong Zhou

Liraglutide, a human glucagon-like peptide (GLP1) analog that partially inhibits dipeptidyl-peptidase 4 (DPP4), can decrease glucose levels and suppress appetite in patients with type 2 diabetes (T2DM). GLP1 and its receptor (GLP1R) also exist in the taste buds of rodents and regulate taste sensitivity. DPP4, a protease, functions in homeostasis of blood glucose, lipids, and body weight. Interactions among GLP1, GLP1R, and DPP4 likely affect taste and food-intake behavior. The aim of the present study was to investigate DPP4 expression in the taste buds of the circumvallate papillae (CV) in T2DM rats, and determine the effects of liraglutide treatment. Rats were divided into diabetic control (T2DM-C), normal control (NC), and liraglutide-treated diabetic (T2DM+LIR) groups. DPP4 localization and gene expression levels were evaluated by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-qPCR), respectively. DPP4 immunoreactive cells were localized in the taste buds of the rat CV. RT-qPCR showed significantly higher expression of Dpp4 mRNA in both the taste buds and hypothalamus of T2DM-C rats compared with NC rats. However, in the T2DM+LIR group, Dpp4 expression differed between the taste buds and hypothalamus, with significantly higher and lower levels compared with the T2DM-C group, respectively. Dpp4 mRNA expression is increased in the taste buds of the CV of T2DM rats. Liraglutide simultaneously upregulated (taste buds) and downregulated (hypothalamus) Dpp4 expression in T2DM rats. Therefore, DPP4 may be closely associated with the anorexigenic signaling and weight loss induced by the treatment of liraglutide in type 2 diabetic patients.


2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Hesam Parsa ◽  
Zahra Moradi-Khaligh ◽  
Sara Rajabi ◽  
Kamal Ranjbar ◽  
Alireza Komaki

AbstractBrain malfunction is common in diabetic patients. On the other hand, a growing body of research points to the beneficial effect of medicinal plants and exercise training on insulin sensitivity and brain function. Therefore, the aim of the present study was to investigate the effect of co-administration of swimming training and Plantago psyllium (mixed with standard pelleted food at a weight ratio of 5%) on learning and memory impairment and glucose tolerance in type 2 diabetic rats. For this purpose, 10 healthy and 40 rats with type 2 diabetes were randomly allocated to five groups: healthy sedentary control group (Con), sedentary diabetic group (D), diabetic group subjected to swimming training (D + Tr), diabetic group receiving P. psyllium (D + Ps), and diabetic group subjected to swimming training and receiving P. psyllium (D + Ps + Tr). Diabetes was induced by a single intraperitoneal injection of nicotinamide (120 mg/kg) and streptozotocin (65 mg/kg) separately with 15 min intervals. Experimental groups were treated with swimming training and P. psyllium independently and simultaneously for 12 weeks. Lipid profile and food intake were measured and also, glucose tolerance was evaluated by glucose area under the curve (AUCg) using an oral glucose tolerance test. Passive avoidance learning (PAL) and memory were evaluated by shuttle box test and cognitive memory was assessed by novel object recognition (NOR) and elevated plus-maze (EPM) tests. Diabetic rats exhibited a significant increase in food intake, lipid profile, and AUCg compared to healthy rats. Step-through latency in the PAL acquisition trial (STL-a) and retention test (STL-r) were significantly lower in diabetic rats than in the control group. In the diabetic group without treatment, time spent in the dark compartment increased compared to the control group in the shuttle box test. Discrimination index and distance traveled reduced in diabetic rats. On the other hand, swimming training and P. psyllium alleviated food intake, lipid profile, and glucose tolerance in diabetic rats. Also, the STL-a, STL-r, discrimination index, and distance travelled in the D + Ps + Tr group were significantly more than the diabetic group. Results showed that 12 weeks of swimming training and receiving P. psyllium improved memory deficit in streptozotocin–nicotinamide-induced type 2 diabetic rats possibly through hypolipidemic and hypoglycemic effects. These results suggest that the administration of swimming training and P. psyllium simultaneously might be an effective intervention for the treatment of diabetes-induced behavioral deficits.


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