scholarly journals GABA administration improves liver function and insulin resistance in offspring of type 2 diabetic rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Azadehalsadat Hosseini Dastgerdi ◽  
Mohammadreza Sharifi ◽  
Nepton Soltani

AbstractThis study investigated the role of GABA in attenuating liver insulin resistance (IR) in type 2 diabetes parents and reducing its risk in their descendants’ liver. Both sexes’ rats were divided into four groups of non-diabetic control, diabetic control (DC), GABA-treated (GABA), and insulin-treated (Ins). The study duration lasted for six months and the young animals followed for four months. Consequently, hyperinsulinemic-euglycemic clamp was performed for all animals. Apart from insulin tolerance test (ITT), serum and liver lipid profile were measured in all groups. Glycogen levels, expression of Foxo1, Irs2, Akt2, and Pepck genes in the liver were assessed for all groups. Overall, GABA improved ITT, increased liver glycogen levels and decreased lipid profile, blood glucose level, and HbA1c in parents and their offspring in compared to the DC group. GIR also increased in both parents and their offspring by GABA. Moreover, the expression of Foxo1, Irs2, Akt2, and Pepck genes improved in GABA-treated parents and their descendants in compared to DC group. Results indicated that GABA reduced liver IR in both parents and their offspring via affecting their liver insulin signaling and gluconeogenesis pathways.

2020 ◽  
Author(s):  
Li Zhang ◽  
Ying-juan Huang ◽  
Jia-pan Sun ◽  
Ting-ying Zhang ◽  
Tao-li Liu ◽  
...  

Abstract Background Caloric restriction (CR), as the only approved scientific method that can retard aging, has become more and more attractive in the treatment of type 2 diabetes mellitus (T2DM) due to increasingly common high calorie diet and sedentary lifestyle. This study aimed to evaluate its role in T2DM treatment and further explored the potential molecular mechanism.Methods A total of 60 male SD rats were used in this study. Diabetes model was induced by 8 weeks of high-fat diet (HFD) followed by a single dose of streptozotocin injection (30mg/kg). Subsequently, the diabetic rats were fed ab libitum of 28g/day (diabetic control) or 20g/day (30% CR regimen) with HFD for 20 weeks. Meanwhile, normal rats had free standard chow diet served as vehicle control. Body mass, plasma glucose, and lipid profile were monitored. After diabetes-related functional tests being done, rats were sacrificed at 10 and 20 weeks, and glucose uptake in fresh muscle were determined. Liver and pancreas were prepared for histopathology and histochemical evaluations, and western blotting and immunofluorescence were applied to detect alterations in AKT/AS160/GLUT4 signaling. Results 30% CR significantly attenuated hyperglycemia and dyslipidemia, leading to alleviation of glucolipotoxicity, thus protected islets secretion, retarding the exhaustion of islets function. Insulin resistance was also markedly ameliorated, as indicated by notably improved insulin tolerance and HOMA-IR. However, glucose uptake in skeletal muscle was not significantly improved, and the up-regulation of AKT/AS160/GLUT4 signaling in muscle induced by 30% CR attenuated gradually over time. However, the consecutive decrease in AKT/AS160/GLUT4 signaling in white adipose tissue was significantly reversed by 30% CR. Conclusion 30% CR could protect islets function from hyperglycemia and dyslipidemia, and improve insulin resistance with probable mechanism related to the up-regulation of AKT/AS160/GLUT4 signaling.


2020 ◽  
Vol Volume 13 ◽  
pp. 2337-2346 ◽  
Author(s):  
Ali Shamsi-Goushki ◽  
Zinat Mortazavi ◽  
Mohammad Ali Mirshekar ◽  
Mahdi Mohammadi ◽  
Nasroallah Moradi-Kor ◽  
...  

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Jan Matczuk ◽  
Anna Zalewska ◽  
Bartłomiej Łukaszuk ◽  
Małgorzata Knaś ◽  
Mateusz Maciejczyk ◽  
...  

In today’s world wrong nutritional habits together with a low level of physical activity have given rise to the development of obesity and its comorbidity, insulin resistance. More specifically, many researches indicate that lipids are vitally involved in the onset of a peripheral tissue (e.g., skeletal muscle, heart, and liver) insulin resistance. Moreover, it seems that diabetes can also induce changes in respect of lipid composition of both the salivary glands and saliva. However, judging by the number of research articles, the salivary glands lipid profile still has not been sufficiently explored. In the current study we aim to assess the changes in the main lipid fractions, namely, triacylglycerols, phospholipids, free fatty acids, and diacylglycerols, in the parotid and the submandibular salivary glands of rats exposed to a 5-week high fat diet regimen. We observed that the high caloric fat diet caused a significant change in the salivary glands lipid composition, especially with respect to PH and TG, but not DAG or FFAs, classes. The observed reduction in PH concentration is an interesting phenomenon frequently signifying the atrophy and malfunctions in the saliva secreting organs. On the other hand, the increased accumulation of TG in the glands may be an important clinical manifestation of metabolic syndrome and type 2 diabetes mellitus.


2021 ◽  
Vol 22 (3) ◽  
pp. 207-219
Author(s):  
Eun Jung Kim ◽  
Eun Young Lee ◽  
Yong-Ho Lee ◽  
Young Ju Choi ◽  
Seok Won Park ◽  
...  

Background: Insulin resistance (IR) and inflammation are closely related to each other and share common pathophysiological and metabolic mechanisms. We aimed to investigate the combined effect of IR and inflammation on comorbidities of type 2 diabetes mellitus (T2DM). Methods: A total 3,758 patients with T2DM were recruited through Huh’s Diabetes Center from January 2003 to June 2009. Insulin sensitivity was measured by a rate constant for plasma glucose disappearance (Kitt , %/min) using short insulin tolerance test. High sensitivity C-reactive protein (hs-CRP) was used as a surrogate for inflammation.Results: Patients with the lowest tertile of Kitt (IR group) showed worse cardio-metabolic parameters while those with the highest tertile of hs-CRP levels had worse cardio-metabolic parameters. The prevalence of metabolic syndrome, fatty liver, albuminuria, and carotid atherosclerosis decreased with Kitt tertile, but increased with hs-CRP tertile. In multiple regression analysis, both Kitt and hs-CRP were independent risk factors for comorbidities of T2DM. In addition, they showed synergistic effects on these comorbidities. Conclusion: Both IR and inflammation were significantly associated with comorbidities of T2DM in a dose dependent manner. In addition, the coexistence of IR and inflammation may synergistically contribute to increased comorbidities of T2DM.


2016 ◽  
Vol 41 (3) ◽  
Author(s):  
Jafar Poodineh ◽  
Alireza Nakhaee

AbstractObjective: Caralluma tuberculata is a succulent plant that grows in some regions of Baluchestan province in Iran, and is widely used by natives as antidiabetic agent. This study evaluates the antidiabetic effects of aerial part suspension of Caralluma tuberculata (SCT) at two doses of 100 and 200 mg/kg and its safety on liver and kidneys of Streptozotocin (STZ)-induced diabetic rats.Methods: Diabetes was rendered via single dose of STZ (60 mg/kg, injected intraperitoneally). Forty eight rats were classified into 6 groups as follow; (I): Normal control, (II): Normal + SCT (200 mg/kg), (III): STZ Diabetic, (IV): STZ + vehicle, (V): STZ + SCT (100 mg/kg), (VI) STZ + SCT (200 mg/kg). The effects of 45 days of treatment with the SCT on oral glucose tolerance test (OGTT), lipid profile, hematological and biochemical parameters evaluated.Results: SCT treated groups exhibited a significant (p<0.05) improvement in abnormalities of OGTT, biochemical and hematological parameters compared with the diabetic control group. Furthermore, SCT at both doses, returned significantly (p<0.01) diabetes-induced changes in lipid profile except HDL-C levels that only, were significantly (p<0.05) increased at dose of 200 mg/kg. There was no significant difference in hematological, liver and kidney parameters between normal control and normal animals receiving SCT.Conclusion: The present results revealed that Caralluma tuberculata could be beneficial for amending hyperglycemia, hyperlipidemia, and hematological changes induced by diabetes. It may also protect the liver and kidneys against complications caused by diabetes without any toxic effects.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A A Momtazi-Borojeni ◽  
M R Jaafari ◽  
E Abdollahi ◽  
M Banach ◽  
A Sahebkar

Abstract Background PCSK9 inhibitors have emerged as an effective lipid-lowering approach. Although the results of available studies suggest a positive association of plasma PCSK9 levels with glycemic parameters and risk of DM, the effects of PCSK9 inhibitors on glucose intolerance and insulin resistance as the key features of DM remain unclear. Purpose The present study was directed to determine effect of vaccine-mediated PCSK9 inhibition on glucose intolerance and insulin resistance in experimental diabetic rats. Methods Nanoliposomal vaccine composing from PCSK9-linked nanoliposome particles mixed in Alum adjuvant was subcutaneously injected four times with bi-weekly intervals in Wistar-Albino rats. Two weeks after the last immunization, vaccinated and non-vaccinated rats were subjected to diabetes experiment induced by single intraperitoneal injection of streptozotocin (STZ). One week after STZ injection, glucose tolerance ability of each animal was evaluated by using oral glucose tolerance test (OGTT) on the overnight fasted rats with glucose dose at 2 g/kg. Two weeks after STZ injection, insulin tolerance test (ITT) viaintraperitoneal injection of insulin (0.8 U/kg) was performed to determine the measure of peripheral utilization of glucose. The plasma concentrations of total cholesterol (TC), LDL-C, HDL-C, and TG were measured. Results Nanoliposomal vaccine exposing PCSK9 peptide was found to provoke high-titers IgG antibody response against PCSK9 in rats, which was associated with the decrease plasma levels and function of plasma PCSK9. During the first week after STZ injection, it was indicated that the fasting blood glucose (FBG) level was 49% (−171.7±35 mg/dL, p<0.0001) lower in the vaccinated diabetic (VD) rats, when compared to the diabetic control (DC) rats. OGTT assessment revealed that the VS rats had significantly improved glucose tolerance ability and recorded significant reduction in the level of blood glucose over the period of 180 min, when compared with the DC rats. Measurement of integrated areas under the glucose curve values demonstrated that blood glucose levels were significantly (p<0.0001) decreased by 34.5% in the VS rats than the DC rats. In addition, ITT analysis showed that after insulin administration blood glucose level was decreased by 49.3% in the VS group compared with the DC group. The VS rats showed significantly lower (−26.65%, p=0.02) plasma LDL-C levels than the DC rats (Figure). Histopathology examination indicated that the pancreatic islet of the VS rats had a slightly decreased population of β-cells and few α-cells. Histopathology examination of the liver tissues of both VS and DC rats exhibited the normal histology with the normal hepatic architecture composed of hepatic lobules with normal central vein. Conclusions PCSK9 inhibition using liposomal vaccine can protect from glucose and insulin tolerance impairments in diabetic rats through an unknown and pancreatic-independent mechanism.


2020 ◽  
Vol 17 (6) ◽  
pp. 147916412096699
Author(s):  
Wenru Li ◽  
Chaonan Zhu ◽  
Tianheng Liu ◽  
Weifang Zhang ◽  
Xu Liu ◽  
...  

Aims: The objective of this study was to explore the effects of epigallocatechin-3-gallate (EGCG) on type 2 diabetes mellitus (T2DM). Main methods: Male Sprague–Dawley rats were allocated into six groups. The control group received a conventional diet. The diabetic group received a high-sucrose high-fat (HSHF) diet for 4 weeks and then was fasted and injected with streptozotocin (STZ); subsequently, the rats received a HSHF diet for another 4 weeks to develop diabetes. The four treatment groups were diabetic rats that received intragastric metformin (500 mg/kg/day) or EGCG (25, 50, and 100 mg/kg/day) for 10 weeks. All groups except the control group received a HSHF diet throughout the experiment. Several biochemical parameters such as fasting blood glucose (FBG), postprandial blood glucose (PBG), liver glycogen, muscle glycogen, fasting serum insulin (FSI), homeostasis model of insulin resistance (HOMA-IR), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFA), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured to assess the effects of EGCG on glycemic control, insulin resistance, lipid profile, and oxidative stress. Furthermore, oxidative stress in pancreatic islet β cells was detected by dihydroethidium staining. Key findings: A HSHF diet and STZ injection induced T2DM, as indicated by changed blood glucose and body weight, which was accompanied by insulin resistance, an altered lipid profile, and oxidative stress. Interestingly, EGCG treatment dose-dependently recovered these indexes. Significance: EGCG successfully ameliorated glycemic control and insulin sensitivity while reducing the lipid profile and oxidative stress in a T2DM rat model.


Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 76 ◽  
Author(s):  
Suresh P. Khadke ◽  
Aniket A. Kuvalekar ◽  
Abhay M. Harsulkar ◽  
Nitin Mantri

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by impaired insulin action and its secretion. The objectives of the present study were to establish an economical and efficient animal model, mimicking pathophysiology of human T2DM to understand probable molecular mechanisms in context with lipid metabolism. In the present study, male Wistar rats were randomly divided into three groups. Animals were fed with high fat diet (HFD) except healthy control (HC) for 12 weeks. After eight weeks, intra peritoneal glucose tolerance test was performed. After confirmation of glucose intolerance, diabetic control (DC) group was injected with streptozotocin (STZ) (35 mg/kg b.w., i.p.). HFD fed rats showed increase (p ≤ 0.001) in glucose tolerance and HOMA-IR as compared to HC. Diabetes rats showed abnormal (p ≤ 0.001) lipid profile as compared to HC. The hepatocyte expression of transcription factors SREBP-1c and NFκβ, and their target genes were found to be upregulated, while PPAR-γ, CPT1A and FABP expressions were downregulated as compared to the HC. A number of animal models have been raised for studying T2DM, but the study has been restricted to only the biochemical level. The model is validated at biochemical, molecular and histopathological levels, which can be used for screening new therapeutics for the effective management of T2DM.


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