Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes

Im, Seung‐Soon; Kang, Seung-Youn; Kim, So-Youn; Kim, Hail; Kim, Jae-Woo; Kim, Kyung‐Sup; Ahn, Young Soo

doi:10.2337/diabetes.54.6.1684

Cited by 111 publications

(101 citation statements)

References 41 publications

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“…This study should be viewed as an important wake up call for the lifestyle that the general population have been gradually adopting, by consuming large amounts of simple sugars in soft drinks [48]. Importantly, exaggerated consumption of these drinks has been associated with an increased risk for T2DM development by about 26% if the average intake is one/two cans a day, or liver of HSu-treated rats, in agreement with previous studies [40][41][42][43][44]. The perturbed liver lipid metabolism that was observed might explain the hypertriglyceridemia present in this prediabetic animal model.…”

Section: Discussionsupporting

confidence: 78%

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet

Burgeiro¹,

Cerqueira²,

Varela-Rodríguez³

et al. 2017

Preprint

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Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water). Body weight, food, and beverage consumption were monitored and glucose, insulin, and lipid profiles were measured. Serum and liver triglyceride concentrations, as well as the expression of genes and proteins involved in lipid biosynthesis were assessed. The insulin-stimulated glucose uptake and isoproterenol-stimulated lipolysis were also measured in freshly isolated adipocytes. Even in the absence of obesity, this rat model already presented the main features of prediabetes, with fasting normoglycemia but reduced glucose tolerance, postprandial hyperglycemia, compensatory hyperinsulinemia, as well as decreased insulin sensitivity (resistance) and hypertriglyceridemia. In addition, impaired hepatic function, including altered gluconeogenic and lipogenic pathways, as well as increased expression of acetyl-coenzyme A carboxylase 1 and fatty acid synthase in the liver, were observed, suggesting that liver glucose and lipid dysmetabolism may play a major role at this stage of the disease.

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Section: Discussionsupporting

confidence: 78%

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet

Burgeiro¹,

Cerqueira²,

Varela-Rodríguez³

et al. 2017

Preprint

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“…This precursor form is then rapidly cleaved, leading to an increased content of the nuclear mature form of SREBP-1c [47]. A high glucose concentration has also been shown in vitro to upregulate SREBP-1c independently of insulin [48].…”

Section: Stimulation Of Fat Synthesismentioning

confidence: 99%

“…This effect may be further amplified by hepatic upregulation of GLUT2 that occurs during hyperglycemia and hypoinsulinemia (characterizing precisely the conditions in type 1 diabetes), mediated by SREBP-1c [48], as described above. This hypothesis could be tested in part by determining the levels of GLUT2 protein and mRNA expression in hepatocytes from humans or animals with type 1 diabetes-induced fatty liver.…”

Section: Hypotheses For Hepatic Steatosis In Type 1 Diabetesmentioning

confidence: 99%

Hepatic Steatosis in Type 1 Diabetes

Regnell

Lernmark

2011

Rev Diabet Stud

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■ AbstractIslet autoimmunity in type 1 diabetes results in the loss of the pancreatic β-cells. The consequences of insulin deficiency in the portal vein for liver fat are poorly understood. Under normal conditions, the portal vein provides 75% of the liver blood supply. Recent studies suggest that non-alcoholic fatty liver disease (NAFLD) may be more common in type 1 diabetes than previously thought, and may serve as an independent risk marker for some chronic diabetic complications. The pathogenesis of NAFLD remains obscure, but it has been hypothesized that hepatic fat accumulation in type 1 diabetes may be due to lipoprotein abnormalities, hyperglycemia-induced activation of the transcription factors carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein 1c (SREBP-1c), upregulation of glucose transporter 2 (GLUT2) with subsequent intrahepatic fat synthesis, or a combination of these mechanisms. Novel approaches to non-invasive determinations of liver fat may clarify the consequences for liver metabolism when the pancreas has ceased producing insulin. This article aims to review the factors potentially contributing to hepatic steatosis in type 1 diabetes, and to assess the feasibility of using liver fat as a prognostic and/or diagnostic marker for the disease. It provides a background and a case for possible future studies in the field.

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“…The limit of detection (LoD= 50 g/ml) and limit of quantification (LoQ=137 g/ml) were determined (signal-noise ratio) and under these analytical parameters, the DCI compound was not detected in this C. ficifolia extract. All NMR spectra were recorded on an Agilent DD2 600 spectrometer (Agilent Technologies, California, USA), at 600 MHz for H NMR, 1 H-1 H COSY, HSQC and HMBC, and at 150 MHz for 13 C NMR in CDCl 3 . Spectrometric analysis was carried out on a gas chromatography-mass spectrometry (GC-MS) (Agilent Technology 6890, California, USA) equipped with a quadrupole mass detector in electron impact mode at 70 eV.…”

Section: Structural Characterization Of the Main Components In C Ficmentioning

confidence: 99%

Chemical Characterization of a Hypoglycemic Extract From Cucurbita Ficifolia Bouche That Induces Liver Glycogen Accumulation in Diabetic Mice.

Jessica¹,

Mario²,

Zamilpa³

et al. 2017

Afr J Tradit Complement Altern Med

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Background: The aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit has demonstrated hypoglycemic effect, which may be attributed to some components in the extract. However, the major secondary metabolites in this fruit have not yet been identified and little is known about its extra-pancreatic action, in particular, on liver carbohydrate metabolism. Therefore, in addition to the isolation and structural elucidation of the principal components in the aqueous extract of C. ficifolia, the aim of this study was to determine whether or not the hypoglycemic effect of the aqueous extract of Cucurbita ficifolia (C. ficifolia) fruit is due to accumulation of liver glycogen in diabetic mice. Materials and Methods:The aqueous extract from fruit of C. ficifolia was fractionated and its main secondary metabolites were purified and chemically characterized (NMR and GC-MS). Alloxan-induced diabetic mice received daily by gavage the aqueous extract (30 days). The liver glycogen content was quantified by spectroscopic method and by PAS stain; ALT and AST by spectrometric method; glycogen synthase, glycogen phosphorylase and GLUT2 by Western blot; the mRNA expression of GLUT2 and glucagon-receptor by RT-PCR; while serum insulin was quantified by ELISA method. A liver histological analysis was also performed by H&E stain. Results: Chemical fingerprint showed five majoritarian compounds in the aqueous extract of C. ficifolia: p-coumaric acid, p-hydroxybenzoic acid, salicin, stigmast-7,2,2-dien-3-ol and stigmast-7-en-3-ol. The histological analysis showed accumulation of liver glycogen. Also, increased glycogen synthase and decreased glycogen phosphorylase were observed. Interestingly, the histological architecture evidenced a liver-protective effect due the extract. Conclusion: Five compounds were identified in C. ficifolia aqueous extract. The hypoglycemic effect of this extract may be partially explained by liver glycogen accumulation. The bioactive compound responsible for the hypoglycemic effect of this extract will be elucidated in subsequent studies.

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Glucose-Stimulated Upregulation of GLUT2 Gene Is Mediated by Sterol Response Element–Binding Protein-1c in the Hepatocytes

Cited by 111 publications

References 41 publications

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet

Glucose and Lipid Dysmetabolism in a Rat Model of Prediabetes Induced by a High-Sucrose Diet

Hepatic Steatosis in Type 1 Diabetes

Chemical Characterization of a Hypoglycemic Extract From Cucurbita Ficifolia Bouche That Induces Liver Glycogen Accumulation in Diabetic Mice.

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