scholarly journals Enhanced Glucose Tolerance and Pancreatic Beta Cell Function by Low Dose Aspirin in Hyperglycemic Insulin-Resistant Type 2 Diabetic Goto-Kakizaki (GK) Rats

2015 ◽  
Vol 36 (5) ◽  
pp. 1939-1950 ◽  
Author(s):  
Layla Amiri ◽  
Annie John ◽  
Jasmin Shafarin ◽  
Ernest Adeghate ◽  
Petrilla Jayaprakash ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Energy Utilization ◽  
Gk Rats ◽  
Insulin Resistant ◽  
Glucose Ingestion ◽  
Anti Inflammatory ◽  
Prevention Of Diabetes

Background/Aim: Type 2 diabetes is the most common metabolic disorder, characterized by insulin resistance and pancreatic islet beta-cell failure. The most common complications associated with type 2 diabetes are hyperinsulinemia, hyperglycemia, hyperlipidemia, increased inflammatory and reduced insulin response. Aspirin (ASA) and other non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with the prevention of diabetes, obesity and related cardiovascular disorders. Aspirin has been used in many clinical and experimental trials for the prevention of diabetes and associated complications. Methods: In this study, five month old Goto-Kakizaki (GK) rats, which showed signs of mild hyperglycemia (fasting blood glucose 80-95 mg/dl vs 55-60 mg/dl Wistar control rats) were used. Two subgroups of GK and Wistar control rats were injected intraperitoneally with 100 mg aspirin/kg body weight/ day for 5 weeks. Animals were sacrificed and blood and tissues were collected after performing glucose tolerance (2 h post 2g IP glucose ingestion) tests in experimental and control groups. Results: Aspirin caused a moderate decrease in hyperglycemia. However, we observed a significant improvement in glucose tolerance after ASA treatment in GK rats compared to the nondiabetic Wistar rats. Also, the ASA treated GK rats exhibited a significant decrease in insulinemia. ASA treatment also caused a marked reduction in the pro-inflammatory prostaglandin, PGE2, which was significantly higher in GK rats. On the other hand, no significant organ toxicity was observed after ASA treatment at this dose and time period. However, the total cholesterol and lipoprotein levels were significantly increased in GK rats, which decreased after ASA treatment. Immunofluorescence staining for insulin/glucagon secreting pancreatic cells showed improved beta-cell structural and functional integrity in ASA-treated rats which was also confirmed by SDS-PAGE and Western blot analysis. Conclusion: The improved glucose tolerance in ASA-treated GK rats may be associated with increased insulin responses due to the anti-inflammatory properties of ASA and enhanced nitric oxide (NO) level which facilitated insulin signaling and energy utilization in target tissues. These results may have implications in determining the therapeutic use of ASA in insulin-resistant type 2 diabetes.

Gluten-free diet increases beta-cell volume and improves glucose tolerance in an animal model of type 2 diabetes

2016 ◽  
Vol 32 (7) ◽  
pp. 675-684 ◽  
Author(s):  
Martin Haupt-Jorgensen ◽  
Karsten Buschard ◽  
Axel K. Hansen ◽  
Knud Josefsen ◽  
Julie Christine Antvorskov
Keyword(s):  
Type 2 Diabetes ◽  
Animal Model ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Cell Volume ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Beta Cell Volume

MG53 marks poor beta cell performance and predicts onset of type 2 diabetes in subjects with different degrees of glucose tolerance.

2021 ◽  
pp. 101292
Author(s):  
Cristina Bianchi ◽  
Francesco Raggi ◽  
Chiara Rossi ◽  
Simona Frontoni ◽  
Riccardo C. Bonadonna ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Beta Cell ◽  
Cell Performance

scholarly journals Increased Circulating Betatrophin Concentrations in Patients with Type 2 Diabetes

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Daniel Espes ◽  
Mats Martinell ◽  
Per-Ola Carlsson
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Beta Cell ◽  
Cell Mass ◽  
Beta Cell Mass ◽  
Insulin Resistant ◽  
Obesity In Mice ◽  
Study Participants ◽  
Diabetes Patients

Betatrophin has recently been described as a key hormone to stimulate beta-cell mass expansion in response to insulin resistance and obesity in mice. The finding has generated an interest in the development of antidiabetic drugs with betatrophin as the active component. However, the circulating levels of betatrophin in patients with type 2 diabetes are not well known. Betatrophin concentrations in plasma of 27 type 2 diabetes patients and 18 gender-, age-, and BMI-matched controls were measured. Study participants were characterized with regard to BMI, waist and hip circumference, blood pressure, and fasting plasma blood lipids, creatinine, glucose, HbA1c, and C-peptide. HOMA2 indices were calculated. Betatrophin was 40% higher in patients with type 2 diabetes (893±80versus639±66 pg/mL). Betatrophin positively correlated with age in the controls and with HbA1c in the type 2 diabetes patients. All study participants were insulin resistant with mean HOMA2B IR in both groups exceeding 2 andHOMA2%S<50%. Control individuals had impaired fasting glucose concentrations. In this report on betatrophin concentrations in type 2 diabetes and insulin resistance, elevated betatrophin levels were measured in the patients with type 2 diabetes. Future studies are clearly needed to delineate the exact role, if any, of betatrophin in regulating human beta-cell mass.

scholarly journals Effects of Resveratrol in Goto-Kakizaki Rat, a Model of Type 2 Diabetes

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2488 ◽  
Author(s):  
Katarzyna Szkudelska ◽  
Marzanna Deniziak ◽  
Iwona Hertig ◽  
Tatiana Wojciechowicz ◽  
Marianna Tyczewska ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Pancreatic Islets ◽  
Lipid Accumulation ◽  
Therapeutic Potential ◽  
Gk Rats ◽  
New Findings

Resveratrol exhibits a pleiotropic, favorable action under various pathological conditions, including type 2 diabetes. However, its anti-diabetic effects in animal models and human trials have not been fully elucidated. The aim of the present study was to determine whether resveratrol is capable of inducing beneficial changes in the Goto-Kakizaki rat, a spontaneous model of diabetes, which in several aspects is similar to type 2 diabetes in humans. Goto-Kakizaki (GK) rats and control Sprague–Dawley (SD) rats were treated intragastrically with resveratrol (20 mg/kg b.w./day) for 10 weeks. Then, a glucose tolerance test was performed and levels of some adipokines in blood were measured. Moreover, lipid contents in skeletal muscle and liver tissues, along with the expression and phosphorylation of pivotal enzymes (AMP—activated protein kinase—AMPK, acetyl-CoA carboxylase—ACC, protein kinase B—Akt) in these tissues were determined. Histology of pancreatic islets was also compared. GK rats non-treated with resveratrol displayed a marked glucose intolerance and had increased lipid accumulation in the skeletal muscle. Moreover, upregulation of the expression and phosphorylation of AMPK, ACC and Akt was shown in the muscle tissue of GK rats. Those rats also had an abnormal structure of pancreatic islets compared with control animals. However, treatment with resveratrol improved glucose tolerance and prevented lipid accumulation in the skeletal muscle of GK rats. This effect was associated with a substantial normalization of expression and phosphorylation of ACC and Akt. In GK rats subjected to resveratrol therapy, the structure of pancreatic islets was also clearly improved. Moreover, blood adiponectin and leptin levels were partially normalized by resveratrol in GK rats. It was revealed that resveratrol ameliorates key symptoms of diabetes in GK rats. This compound improved glucose tolerance, which was largely linked to beneficial changes in skeletal muscle. Resveratrol also positively affected pancreatic islets. Our new findings show that resveratrol has therapeutic potential in GK rats.

scholarly journals Lupinus mutabilis Extract Exerts an Anti-Diabetic Effect by Improving Insulin Release in Type 2 Diabetic Goto-Kakizaki Rats

Nutrients ◽  
2018 ◽  
Vol 10 (7) ◽  
pp. 933 ◽  
Author(s):  
Silvia Zambrana ◽  
Lena Lundqvist ◽  
Orlando Mamani ◽  
Sergiu-Bogdan Catrina ◽  
Eduardo Gonzales ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Insulin Release ◽  
Gk Rat ◽  
Gk Rats ◽  
Rat Islets ◽  
Lupinus Mutabilis

Lupinus mutabilis (LM) is a legume part of Bolivian traditional diet that has a nutraceutical property reducing blood glucose levels. The prevalence of type 2 diabetes is increasing worldwide thus; the search for novel anti-diabetic drugs is needed. Based on its traditional use, we evaluated the anti-diabetic effect of LM in the spontaneously diabetic Goto-Kakizaki (GK) rat, a model of type 2 diabetes and in Wistar (W) rats as healthy control. LM seeds hydroethanolic extract, analyzed by gas chromatography-mass spectrometry and high-performance liquid chromatography-high resolution mass spectrometry, is a complex mixture of volatile and non-volatile components. A single oral administration of LM extract (2000 mg/kg b.w.) improved glucose tolerance during the oral glucose tolerance test (OGTT) (30–120 min) in GK and W rats (p < 0.0001). The long-term treatment with LM (1000 mg/kg b.w.), for 21 days, improved the area under the curve (AUC) of glucose during OGTT at day 20, in both GK (p < 0.01) and W rats (p < 0.01). The HbA1c (GK rats, p < 0.05 and W rats, p < 0.0001) and the non-fasting glucose (GK rats, p < 0.05) were also reduced. LM increased both serum insulin levels (2.4-fold in GK rats and 2.5-fold W rats), and the glucose-induced (16.7 mM glucose) insulin release in isolated islets from treated animals (6.7-fold in GK rats, and 6.6-fold in W rats). Moreover, LM (10 mg/mL) stimulated in vitro glucose induced (16.7 mM glucose) insulin release in batch incubated GK and W rat islets (p < 0.0001). In perifused GK rat islets, insulin release in 16.7 mM glucose was increased 95.3-fold compared to untreated islets (p < 0.0001), while no significant differences were found in perifused W rat islets. The LM mechanism of action, evaluated using inhibitory compounds of the insulin secretion pathway, showed that LM-dependent insulin secretion was reduced 42% by diazoxide (p < 0.001), 70% by nifedipine (p < 0.001), 86.7% by H89 (p < 0.0001), 70.8% by calphostine-C (p < 0.0001) and 93% by pertussis toxin (p < 0.0001). A similar effect was observed in W rats islets. Our findings provide evidence that LM has an anti-diabetic effect through stimulation of insulin release. The effect is-dependent on L-type calcium channel, protein kinase A and C systems, and G protein-coupled exocytosis and is partially mediated by K-ATP channels.

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