scholarly journals High Energy Intake Induced Overexpression of Transcription Factors and Its Regulatory Genes Involved in Acceleration of Hepatic Lipogenesis: A Rat Model for Type 2 Diabetes

Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 76 ◽  
Author(s):  
Suresh P. Khadke ◽  
Aniket A. Kuvalekar ◽  
Abhay M. Harsulkar ◽  
Nitin Mantri
Keyword(s):  
Type 2 Diabetes ◽  
Transcription Factors ◽  
Glucose Tolerance ◽  
Molecular Mechanisms ◽  
Target Genes ◽  
High Energy ◽  
Tolerance Test ◽  
Diabetic Control ◽  
Ppar Γ

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.

scholarly journals Adipocyte PU.1 knockout promotes insulin sensitivity in HFD-fed obese mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Denise E. Lackey ◽  
Felipe C. G. Reis ◽  
Roi Isaac ◽  
Rizaldy C. Zapata ◽  
Dalila El Ouarrat ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Target Genes ◽  
Obese Mice ◽  
Tissue Macrophage

Abstract Insulin resistance is a key feature of obesity and type 2 diabetes. PU.1 is a master transcription factor predominantly expressed in macrophages but after HFD feeding PU.1 expression is also significantly increased in adipocytes. We generated adipocyte specific PU.1 knockout mice using adiponectin cre to investigate the role of PU.1 in adipocyte biology, insulin and glucose homeostasis. In HFD-fed obese mice systemic glucose tolerance and insulin sensitivity were improved in PU.1 AKO mice and clamp studies indicated improvements in both adipose and liver insulin sensitivity. At the level of adipose tissue, macrophage infiltration and inflammation was decreased and glucose uptake was increased in PU.1 AKO mice compared with controls. While PU.1 deletion in adipocytes did not affect the gene expression of PPARg itself, we observed increased expression of PPARg target genes in eWAT from HFD fed PU.1 AKO mice compared with controls. Furthermore, we observed decreased phosphorylation at serine 273 in PU.1 AKO mice compared with fl/fl controls, indicating that PPARg is more active when PU.1 expression is reduced in adipocytes. Therefore, in obesity the increased expression of PU.1 in adipocytes modifies the adipocyte PPARg cistrome resulting in impaired glucose tolerance and insulin sensitivity.

scholarly journals Habenula lesions improve glucose metabolism in rats with type 2 diabetes by increasing insulin sensitivity and inhibiting gluconeogenesis

2020 ◽  
Vol 8 (1) ◽  
pp. e001250
Author(s):  
Peng Qu ◽  
Yachun Wang ◽  
Lei Liu ◽  
Mengmeng Qi ◽  
Yimeng Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Nervous System ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Sham Group ◽  
Adrenal Glands ◽  
Tolerance Test ◽  
Lesion Group

IntroductionThe habenular nucleus (Hb), a famous relay station in the midbrain, is vital for controlling many physiological functions of vertebrates. The role of Hb in the pathogenesis of depression has been thoroughly studied, but whether it functions in the pathogenesis of diabetes remains unknown. In this study, we found that Hb lesions could improve glucose metabolism in type 2 diabetes mellitus (T2DM) by inhibiting the peripheral sympathetic nervous system and hepatic glucose production.Research design and methodsT2DM rats were induced by a high-carbohydrate and fat diet combined with streptozotocin. Electrical lesion method was applied to suppress the function of Hb. Serum and tissue samples of rats in the control group, T2DM group, sham group, and Hb lesion group were detected by ELISA, western blotting, and biochemical methods.ResultsCompared with the sham group, the expression levels of AMPK phosphorylation and insulin receptor (IR) were significantly increased, whereas glucose-6-phosphatase and phosphoenolpyruvate carboxylated kinase were reduced in the liver of the Hb lesion group. In the glucose tolerance test and pyruvate tolerance test, the lesion group showed stronger glucose tolerance and lower hepatic gluconeogenesis than the sham. These results suggest that Hb lesions not only effectively increase insulin sensitivity and improve insulin resistance but also inhibit gluconeogenesis in T2DM rats. Moreover, Hb lesions increase the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase B, glucocorticoid receptor, and IR in the hippocampus. In this study, we also found that Hb lesions increase the content of acetylcholine in the adrenal glands and reduce the content of epinephrine in both the adrenal glands and the liver, which may be the main reason for the Hb lesions to regulate glucose metabolism in the liver.ConclusionHb is an important neuroanatomical target for the regulation of glucose metabolism in the central nervous system of diabetic rats.

Effect of hypoxic exercise on glucose tolerance in healthy and prediabetic adults

2021 ◽  
Vol 320 (1) ◽  
pp. E43-E54
Author(s):  
Estelle De Groote ◽  
Florian A. Britto ◽  
Estelle Balan ◽  
Geoffrey Warnier ◽  
Jean-Paul Thissen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Metabolism ◽  
Glucose Tolerance ◽  
Healthy Subjects ◽  
Molecular Mechanisms ◽  
Acute Exercise ◽  
Normobaric Hypoxia ◽  
Hypoxic Exercise

The molecular mechanisms involved in glucose tolerance after acute exercise in hypoxia have not yet been elucidated in human. Due to the reversible character of their status, prediabetic individuals are of particular interest for preventing the development of type 2 diabetes. The present study is the first to investigate muscle molecular mechanisms during exercise and glucose metabolism after exercise in prediabetic and healthy subjects exercising in normoxia and normobaric hypoxia.

scholarly journals A novel 11β-HSD1 inhibitor improves diabesity and osteoblast differentiation

2014 ◽  
Vol 52 (2) ◽  
pp. 191-202 ◽  
Author(s):  
Ji Seon Park ◽  
Su Jung Bae ◽  
Sik-Won Choi ◽  
You Hwa Son ◽  
Sung Bum Park ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Osteoblast Differentiation ◽  
Tolerance Test ◽  
Model Systems ◽  
C2c12 Cells ◽  
Therapeutic Window ◽  
Oral Glucose

Selective inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) have considerable potential as treatment for osteoporosis as well as metabolic syndrome including type 2 diabetes mellitus. Here, we investigated the anti-diabetic, anti-adipogenic, and anti-osteoporotic activity of KR-67500, as a novel selective 11β-HSD1 inhibitor. Cellular 11β-HSD1 activity was tested based on a homogeneous time-resolved fluorescence method. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) levels were measured in diet-induced obese (DIO)-C57BL/6 mice administered KR-67500 (50 mg/kg per day, p.o.) for 28 days and, additionally, its anti-diabetic effect was evaluated by OGTT and ITT. Thein vitroanti-adipogenic effect of KR-67500 was determined by Oil Red O Staining. Thein vitroanti-osteoporotic activity of KR-67500 was evaluated using bone morphogenetic protein 2 (BMP2)-induced osteoblast differentiation and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model systems. KR-67500 improved thein vivoglucose tolerance and insulin sensitivity in DIO-C57BL/6 mice. KR-67500 suppressed cortisone-induced differentiation of 3T3-L1 cells into adipocytes. KR-67500 enhanced BMP2-induced osteoblastogenesis in C2C12 cells and inhibited RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages. KR-67500, a new selective 11β-HSD1 inhibitor, may provide a new therapeutic window in the prevention and/or treatment of type 2 diabetes, obesity, and/or osteoporosis.

Regulation of glucagon secretion by incretin-like hormone family in the patients at risk of developing type 2 diabetes mellitus

2014 ◽  
Vol 60 (1) ◽  
pp. 32-35
Author(s):  
E A Shestakova ◽  
A V Ilyin ◽  
A D Deev ◽  
M V Shestakova ◽  
I I Dedov
Keyword(s):  
Type 2 Diabetes ◽  
High Risk ◽  
Glucose Tolerance ◽  
Glucagon Secretion ◽  
Tolerance Test ◽  
Normal Glucose Tolerance ◽  
High Risk Group ◽  
Oral Glucose ◽  
Glucose Load

The study included 127 patients with type 2 diabetes (T2D) risk factors, who underwent oral glucose tolerance test (75 g glucose) with pancreatic and incretin hormones estimated in fasting state, at 30 and 120 minutes after glucose load. According to the test results the population was divided into 3 groups: group with normal glucose tolerance (NGT), group with high risk of diabetes developing (impaired glucose tolerance (IGT) and impaired fasting glycemia (IFG)) and newly-diagnosed T2D. The stimulated glucagon secretion was suppressed in NGT group, whereas in T2D patients there was an increase in glucagon levels at 30 min after the glucose load. Within high risk group the area under curve (AUC) of glucagon secretion was significantly elevated in IFG patients comparing to IGT (0,52 vs 0,07 ng·ml-1·min-1, р=0,0005). AUC of glucagon secretion was positively related only to fasting glucagon-like peptide 2 (GLP-2) level (r=0,61, р=0,0001), that suggests glucagonotropic properties for GLP-2. We conclude that glucagon stimulation by GLP-2 may play a role in decreased glucagon suppression in T2D patients and IFG state development.

scholarly journals Assessment of insulin secretion from the oral glucose tolerance test in white patients with type 2 diabetes

Diabetes Care ◽  
2000 ◽  
Vol 23 (9) ◽  
pp. 1440-1441 ◽  
Author(s):  
M. Stumvoll ◽  
A. Mitrakou ◽  
W. Pimenta ◽  
T. Jenssen ◽  
H. Yki-Jarvinen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Secretion ◽  
Glucose Tolerance ◽  
Oral Glucose Tolerance Test ◽  
Glucose Tolerance Test ◽  
Tolerance Test ◽  
Oral Glucose ◽  
Oral Glucose Tolerance ◽  
White Patients
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