Abstract 2436: Acute Metformin Treatment Worsens Short-term Stroke Outcome: Comparison Of Underlying Mechanisms In Control And Type 2 Diabetic Rats

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Weiguo Li ◽  
Connie Chung ◽  
Roshini Prakash ◽  
Dhruv Chawla ◽  
Maribeth Johnson ◽  
...  

Background: Admission hyperglycemia aggravates neurovascular injury and worsens outcome in acute ischemic stroke (AIS). Current stroke guidelines recommend glycemic control as an important therapeutic strategy to prevent cerebrovascular complications. We have previously shown that chronic glucose control with metformin prior to AIS prevents cerebrovascular remodeling, reduces hemorrhagic transformation (HT), and improves neurological outcome. The goal of this study was to test the hypothesis that acute glucose control in diabetes prior to AIS will also provide neurovascular protection and improve functional outcome. Methods: Ten-week-old male control and type 2 diabetic Goto-Kakizaki (GK) rats (n=6-9 each group) were treated with or without metformin (300mg/kg/day in drinking water) for 3 days prior to stroke. Infarct size, edema ratio (% edema/infarct), and HT frequency and severity were evaluated in all groups after 3 hr middle cerebral artery occlusion (MCAO) and 21 hr reperfusion. AMPK activity and lactate levels--biomarkers of ischemic brain metabolism--were also measured. Results: Compared to controls, metformin treatment decreased blood glucose levels in diabetic animals (160.4±36.5 vs. 120.1±31.1 mg/dL, p<0.0001). Metformin treatment decreased edema ratio in GKs (0.90±0.71 vs. 1.55±0.70, p<0.05), but increased infarct size (23.3±17.5 vs. 12.5±9.5%, p<0.05). Untreated diabetic rats had lower composite scores for neurological tests (3.8±2.4 vs. 5.9±1.2, p<0.05), indicating worse outcome. Metformin treatment worsened this deficit in both diabetic and control animals (2.4±1.6 vs. 1.9±1.0, p=0.0008). AMPK activity was increased only in metformin-treated GK rats while lactate levels were increased in both groups (p<0.05). Results are expressed as mean ± SD. Conclusion: Worsening of stroke outcome by acute metformin treatment is associated with increased lactate accumulation in both control and diabetic rats. Increased infarct size in diabetic but not control rats may be due to greater AMPK activation in diabetes. Whether this effect is specific to metformin or general to acute glycemic control needs to be confirmed with other glucose control measures.

2017 ◽  
Vol 42 (4) ◽  
pp. 377-383 ◽  
Author(s):  
Chika Ifeanyi Chukwuma ◽  
Md. Shahidul Islam

Previous studies have suggested that sorbitol, a known polyol sweetener, possesses glycemic control potentials. However, the effect of sorbitol on intestinal glucose absorption and muscle glucose uptake still remains elusive. The present study investigated the effects of sorbitol on intestinal glucose absorption and muscle glucose uptake as possible anti-hyperglycemic or glycemic control potentials using ex vivo and in vivo experimental models. Sorbitol (2.5% to 20%) inhibited glucose absorption in isolated rat jejuna (IC50= 14.6% ± 4.6%) and increased glucose uptake in isolated rat psoas muscle with (GU50= 3.5% ± 1.6%) or without insulin (GU50= 7.0% ± 0.5%) in a concentration-dependent manner. Furthermore, sorbitol significantly delayed gastric emptying, accelerated digesta transit, inhibited intestinal glucose absorption, and reduced blood glucose increase in both normoglycemic and type 2 diabetic rats after 1 h of coingestion with glucose. Data of this study suggest that sorbitol exhibited anti-hyperglycemic potentials, possibly via increasing muscle glucose uptake ex vivo and reducing intestinal glucose absorption in normal and type 2 diabetic rats. Hence, sorbitol may be further investigated as a possible anti-hyperglycemic sweetener.


Nutrition ◽  
2019 ◽  
Vol 63-64 ◽  
pp. 45-50 ◽  
Author(s):  
Naoki Horii ◽  
Natsuki Hasegawa ◽  
Shumpei Fujie ◽  
Masataka Uchida ◽  
Keiko Iemitsu ◽  
...  

2021 ◽  
Vol 14 (2) ◽  
pp. 144
Author(s):  
Ahmed A. E. Mourad ◽  
Ahmed E. Khodir ◽  
Sameh Saber ◽  
Mai A. E. Mourad

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have emerged as anti-hyperglycemic agents that improve glycemic control in type 2 diabetic patients, either as monotherapy or in combination with other antidiabetic drugs. Methods: A novel series of dihydropyrimidine phthalimide hybrids was synthesized and evaluated for their in vitro and in vivo DPP-4 inhibition activity and selectivity using alogliptin as reference. Oral glucose tolerance test was assessed in type 2 diabetic rats after chronic treatment with the synthesized hybrids ± metformin. Cytotoxicity and antioxidant assays were performed. Additionally, molecular docking study with DPP-4 and structure activity relationship of the novel hybrids were also studied. Results: Among the synthesized hybrids, 10g, 10i, 10e, 10d and 10b had stronger in vitro DPP-4 inhibitory activity than alogliptin. Moreover, an in vivo DPP-4 inhibition assay revealed that 10g and 10i have the strongest and the most extended blood DPP-4 inhibitory activity compared to alogliptin. In type 2 diabetic rats, hybrids 10g, 10i and 10e exhibited better glycemic control than alogliptin, an effect that further supported by metformin combination. Finally, 10j, 10e, 10h and 10d had the highest radical scavenging activity in DPPH assay. Conclusions: Hybrids 10g, 10i and 10e are potent DPP-4 inhibitors which may be beneficial for T2DM treatment.


Author(s):  
Pushpita De ◽  
Shaheen Banu ◽  
Diviya Muthukumar

Background: The aim of this study is to shed light on the patients ‘knowledge, expectations and attitudes with regards to glucose control, and to understand the barriers to achieving good glucose control among south Indian patients with type 2 diabetes.Methods: A cross-sectional study was conducted among 76 type 2 diabetic patients in this study. Patients’ information such as sociodemographic characteristics, family history of diabetes, diabetes duration, medication adherence, dietary pattern, physical activity was obtained through interview. Anthropometric details were noted during the interview. All available last readings for fasting blood sugar, post prandial blood sugar and glycosylated hemoglobin were abstracted from patients’ records.Results: A total of 76 patients were enrolled in the study. The overall mean (SD) duration of the disease was 9±7.02 years. 63% had HbA1c ≥7%, which is categorized as a poor glycemic control. 43% of the subjects had poor glucose control who did not follow healthy eating plans. 84% of the patients did participate in physical exercise but did not follow as recommended. 67% of the patients have poor knowledge about glucose control.Conclusions: The main results indicate that glycemic control in type 2 diabetes is generally poor. Longer duration of diabetes and not adherent to diabetes self-care management behaviors were associated with poor glycemic control. Therefore, a balanced approach to improve awareness about diabetes and its control both among patients and the medical fraternity is urgent need of the hour in India.


2020 ◽  
Vol 11 ◽  
Author(s):  
Lamiaa A. Ahmed ◽  
Nesma A. Shiha ◽  
Amina S. Attia

Type 2 diabetes mellitus (T2DM) has been recognized as a known risk factor for cardiovascular diseases. Additionally, studies have shown the prevalence of depression among people with diabetes. Thus, the current study aimed to investigate the possible beneficial effects of escitalopram, a selective serotonin reuptake inhibitor, on metabolic changes and cardiac complications in type 2 diabetic rats. Diabetes was induced by feeding the rats high fat-high fructose diet (HFFD) for 8 weeks followed by a subdiabetogenic dose of streptozotocin (STZ) (35 mg/kg, i. p.). Treatment with escitalopram (10 mg/kg/day; p. o.) was then initiated for 4 weeks. At the end of the experiment, electrocardiography was performed and blood samples were collected for determination of glycemic and lipid profiles. Animals were then euthanized and heart samples were collected for biochemical and histopathological examinations. Escitalopram alleviated the HFFD/STZ-induced metabolic and cardiac derangements as evident by improvement of oxidative stress, inflammatory, fibrogenic and apoptotic markers in addition to hypertrophy and impaired conduction. These results could be secondary to its beneficial effects on the glycemic control and hence the reduction of receptor for advanced glycation end products content as revealed in the present study. In conclusion, escitalopram could be considered a favorable antidepressant medication in diabetic patients as it seems to positively impact the glycemic control in diabetes in addition to prevention of its associated cardiovascular complications.


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