Using positron emission tomography to study human ketone body metabolism: A review

Ketone bodies – 3-hydroxybutyrate and acetoacetate – are important fuel substrates, which can be oxidized by most tissues in the body. They are synthesized in the liver and are derived from fatty acids released from adipose tissue. Intriguingly, under conditions of stress such as fasting, arterio-venous catheterization studies have shown that the brain switches from the use of almost 100% glucose to the use of > 50–60% ketone bodies. A similar adaptive mechanism is observed in the heart, where fasting induces a shift toward ketone body uptake that provides the myocardium with an alternate fuel source and also favorably affects myocardial contractility. Within the past years there has been a renewed interest in ketone bodies and the possible beneficial effects of fasting/semi-fasting/exercising and other “ketogenic” regimens have received much attention. In this perspective, it is promising that positron emission tomography (PET) techniques with isotopically labeled ketone bodies, fatty acids and glucose offer an opportunity to study interactions between ketone body, fatty acid and glucose metabolism in tissues such as the brain and heart. PET scans are non-invasive and thus eliminates the need to place catheters in vascular territories not easily accessible. The short half-life of e.g. 11C-labeled PET tracers even allows multiple scans on the same study day and reduces the total radiation burden associated with the procedure. This short review aims to give an overview of current knowledge on ketone body metabolism obtained by PET studies and discusses the methodological challenges and perspectives involved in PET ketone body research.     

Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized.     

Soy β-conglycinin improves glucose uptake in skeletal muscle and ameliorates hepatic insulin resistance in Goto-Kakizaki rats

Although the underlying mechanism is unclear, β-conglycinin (βCG), the major component of soy proteins, regulates blood glucose levels. Here, we hypothesized that consumption of βCG would normalize blood glucose levels by ameliorating insulin resistance and stimulating glucose uptake in skeletal muscles. To test our hypothesis, we investigated the antidiabetic action of βCG in spontaneously diabetic Goto-Kakizaki (GK) rats. Our results revealed that plasma adiponectin levels and adiponectin receptor 1 messenger RNA expression in skeletal muscle were higher in βCG-fed rats than in casein-fed rats. Phosphorylation of adenosine monophosphate–activated protein kinase (AMP kinase) but not phosphatidylinositol-3 kinase was activated in βCG-fed GK rats. Subsequently, βCG increased translocation of glucose transporter 4 to the plasma membrane. Unlike the results in skeletal muscle, the increase in adiponectin receptor 1 did not lead to AMP kinase activation in the liver of βCG-fed rats. The down-regulation of sterol regulatory element-binding factor 1, which is induced by low insulin levels, promoted the increase in hepatic insulin receptor substrate 2 expression. Based on these findings, we concluded that consumption of soy βCG improves glucose uptake in skeletal muscle via AMP kinase activation and ameliorates hepatic insulin resistance and that these actions may help normalize blood glucose levels in GK rats.     

Optimization of GPR40 Agonists for Type 2 Diabetes

相似文献   

大黄素、小檗碱对HepG2细胞胰岛素抵抗的预防作用研究

目的：研究大黄素、小檗碱对HepG2细胞产生胰岛素抵抗的预防作用及机制。方法：首先用MTT法筛选大黄素、小檗碱作用于HepG2细胞的实验浓度,然后用软脂酸诱导HepG2细胞,同时分别加入大黄素、小檗碱干预,并设正常组、对照组进行比较,通过葡萄糖氧化酶法、蒽酮法、RT-PCR法,观察大黄素、小檗碱对HepG2细胞上糖代谢及瘦素长型受体、短型受体mRNA表达水平的影响。结果：对照组成为具有胰岛素抵抗的HepG2细胞,且细胞上瘦素长型及短型受体mRNA的表达水平较正常组显著下降（P < 0.01）;而大黄素、小檗碱组培养液中葡萄糖含量、细胞内糖原含量以及细胞上瘦素长型及短型受体mRNA的表达水平较正常组无明显改变（P > 0.05）。结论：大黄素、小檗碱均能预防HepG2细胞产生胰岛素抵抗,这一作用与它们影响 HepG2细胞上糖代谢及瘦素受体mRNA表达水平有关。     

Sterol regulatory element-binding protein-1c knockdown protected INS-1E cells from lipotoxicity

Objective: The reduction in insulin secretory capacity and β-cell mass has been attributed, at least partially, to lipotoxicity, which may contribute to the development of type 2 diabetes. Chronic free fatty acids (FFA) exposure impairs pancreatic β-cell function and induces β-cell apoptosis. This study is to elucidate the underlying molecular mechanisms.
Research design and methods: We exposed INS-1E pancreatic β-cell line to palmitate or oleate, and measured the glucose stimulated insulin secretion (GSIS). The effect of FFA on sterol regulatory element-binding protein (SREBP)-1c lipogenic pathway, and expression of genes involved in β-cell functions, including AMPK (AMP-activated protein kinase), UCP-2 (uncoupling protein-2), IRS-2 (insulin receptor substrate-2), PDX-1 (pancreatic duodenal homeobox-1), GLUT-2 (glucose transporter-2) and B cell lymphoma/leukaemia-2 (Bcl-2) were investigated. Apoptosis of these exposed cells was determined by MitoCapture, Annexin V-Cy3 or terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay. Cell lipid accumulation was measured by oil red O staining or TG extraction. Also SREBP-1c expression knockdown were used.
Results: FFA treatment resulted in SREBP-1c overexpression, impaired GSIS, lipid accumulation, apoptosis of INS-1E cells. In addition, the expression of lipogenic genes and UCP-2 were upregulated, but AMPK, IRS-2, PDX-1, GLUT-2 and Bcl-2 were downregulated in the exposed cells. However, these lipotoxic effects of FFA were largely prevented by induction of a SREBP-1c small interfering RNA.
Conclusions: These data suggest a strong correlation between FFA treatment and SREBP-1c activation in INS-1E cells. SREBP-1c might be a major factor responsible for β-cell lipotoxicity, and SREBP-1c knockdown could protect INS-1E cells from lipotoxicity, which is implicating a therapeutic potential for treating diabetes related to lipotoxicity.     

降脂清肝方及其拆方对脂肪肝家鸭FFA、LPL、HL的影响

目的:探讨降脂清肝方及其拆方对脂肪肝家鸭游离脂肪酸(FFA)、脂蛋白脂酶(LPL)、肝脂酶(HL)的影响。方法:对高糖饲料填饲的家鸭给降脂清肝方及拆方,观察各组家鸭FFA、LPL、HL的变化。结果:全方组和丹姜组血清FFA水平明显降低(P<0.01),全方组、丹姜组肝组织LPL明显高于空白组、模型组(P<0.01),菏泽组亦高于空白组、模型组(P<0.05),各组肝组织HL无显著差异、丹姜组有升高趋势。结论:降脂清肝方和丹参、姜黄可显著降低血清FFA、升高肝组织LPL指标,丹参、姜黄还有升高肝组织HL的趋势,丹参、姜黄可能为降脂的主要成分。     

FFA在Eales病激光治疗中的作用探讨

目的探讨荧光素眼底血管造影(FFA)在视网膜静脉周围炎(Eales病)激光治疗中的作用。方法按病例选择标准筛选60例(108眼)经临床确诊为Eales病患者,随机分为研究组和对照组。研究组用FFA检查后选择眼底病变区域行激光光凝。对照组不经FFA检查,直接行视网膜光凝。6个月后两组病例均用FFA检查视网膜、血管病变是否好转,比较治疗前后视力、眼底变化、视野改变,评价治疗效果。结果研究组33例58眼Eales病患眼治疗有效54眼(93.1%),无效4眼(6.9%)。对照组27例50眼Eales病患眼治疗有效34眼(68.0%),无效16眼(32.0%)。研究组58眼激光光凝后均无视野改变,对照组50眼激光光凝后均有不同程度视野缩小。结论依据FFA检查对Eales病激光光凝,治疗效果优于不经FFA检查直接行视网膜光凝。FFA为进一步探讨Eales病的发病机理,为临床治疗Eales病提供重要的指导依据。