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Gary W. Cline 대한당뇨병학회 2011 Diabetes and Metabolism Journal Vol.35 No.5
The pancreatic islet β-cell is uniquely specialized to couple its metabolism and rates of insulin secretion with the levels of circulating nutrient fuels, with the mitochondrial playing a central regulatory role in this process. In the β-cell, mitochondrial activation generates an integrated signal reflecting rates of oxidativephosphorylation, Kreb’s cycle flux, and anaplerosis that ultimately determines the rate of insulin exocytosis. Mitochondrial activation can be regulated by proton leak and mediated by UCP2, and by alkalinization to utilize the pH gradient to drive substrate and ion transport. Converging lines of evidence support the hypothesis that substrate cycles driven by rates of Kreb’s cycle flux and by anaplerosis play an integral role in coupling responsive changes in mitochondrial metabolism with insulin secretion. The components and mechanisms that account for the integrated signal of ATP production, substrate cycling, the regulation of cellular redox state, and the production of other secondary signaling intermediates are operative in both rodent and human islet β-cells.
Nonhuman primate model in mammary gland biology and neoplasia research
Dewi Fitriya N.,Cline J. Mark 한국실험동물학회 2021 Laboratory Animal Research Vol.37 No.1
Research on breast cancer pathogenesis, prevention and drug development remains an important field as this disease is still one of the leading causes of cancer death worldwide. Nonhuman primates, particularly macaque species, may serve as a highly translational animal model in breast cancer studies due to their similarity with humans in genetics, anatomy, reproductive and endocrine physiology including mammary gland development profile. The use of nonhuman primates in biomedical research, however, requires high ethical standards and an increasing expectation to improve strategies to replace, reduce and refine their use. Here, we discuss some key features of nonhuman primate mammary gland biology relevant to their strengths and limitations as models in studies of breast development and cancer risk.
Mitochondrial phosphate transport during nutrient stimulation of INS-1E insulinoma cells
Quan, X.,Das, R.,Xu, S.,Cline, G.W.,Wiederkehr, A.,Wollheim, C.B.,Park, K.S. North-Holland 2013 Molecular and cellular endocrinology Vol.381 No.1
Here, we have investigated the role of inorganic phosphate (P<SUB>i</SUB>) transport in mitochondria of rat clonal β-cells. In α-toxin-permeabilized INS-1E cells, succinate and glycerol-3-phosphate increased mitochondrial ATP release which depends on exogenous ADP and P<SUB>i</SUB>. In the presence of substrates, addition of P<SUB>i</SUB> caused mitochondrial matrix acidification and hyperpolarisation which promoted ATP export. Dissipation of the mitochondrial pH gradient or pharmacological inhibition of P<SUB>i</SUB> transport blocked the effects of P<SUB>i</SUB> on electrochemical gradient and ATP export. Knock-down of the phosphate transporter P<SUB>i</SUB>C, however, neither prevented P<SUB>i</SUB>-induced mitochondrial activation nor glucose-induced insulin secretion. Using <SUP>31</SUP>P NMR we observed reduction of P<SUB>i</SUB> pools during nutrient stimulation of INS-1E cells. Interestingly, P<SUB>i</SUB> loss was less pronounced in mitochondria than in the cytosol. We conclude that matrix alkalinisation is necessary to maintain a mitochondrial P<SUB>i</SUB> pool, at levels sufficient to stimulate energy metabolism in insulin-secreting cells beyond its role as a substrate for ATP synthesis.
Xiaoxiao Li,Jing Luo,Pon Velayutham Anandh Babu,Wei Zhang,Elizabeth Gilbert,Mark Cline,Ryan McMillan,Matthew Hulver,Hana Alkhalidy,Wei Zhen,Haiyan Zhang,Dongmin Liu 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.12
Obesity and diabetes are growing health problems worldwide. In this study, dietary provision of Chinese ginseng (0.5 g/kg diet) prevented body weight gain in high-fat (HF) diet-fed mice. Dietary ginseng supplementation reduced body fat mass gain, improved glucose tolerance and whole body insulin sensitivity, and prevented hypertension in HF dietinduced obese mice. Ginseng consumption led to reduced concentrations of plasma insulin and leptin, but had no effect on plasma adiponectin levels in HF diet-fed mice. Body temperature was higher in mice fed the ginseng-supplemented diet but energy expenditure, respiration rate, and locomotive activity were not significantly altered. Dietary intake of ginseng increased fatty acid oxidation in the liver but not in skeletal muscle. Expression of several transcription factors associated with adipogenesis (C/EBPa and PPARc) were decreased in the adipose tissue of HF diet-fed mice, effects that were mitigated in mice that consumed the HF diet supplemented with ginseng. Abundance of fatty acid synthase (FASN) mRNA was greater in the adipose tissue of mice that consumed the ginseng-supplemented HF diet as compared with control or un-supplemented HF diet-fed mice. Ginseng treatment had no effect on the expression of genes involved in the regulation of food intake in the hypothalamus. These data suggest that Chinese ginseng can potently prevent the development of obesity and insulin resistance in HF diet-fed mice.
Measurement of the neutrino velocity with the ICARUS detector at the CNGS beam
ICARUS Collaboration,Antonello, M.,Aprili, P.,Baiboussinov, B.,Baldo Ceolin, M.,Benetti, P.,Calligarich, E.,Canci, N.,Centro, S.,Cesana, A.,Cieslik, K.,Cline, D.B.,Cocco, A.G.,Dabrowska, A.,Dequal, D. North-Holland Pub. Co 2012 Physics letters: B Vol.713 No.1
At the end of the 2011 run, the CERN CNGS neutrino beam has been briefly operated in lower intensity mode with ∼10<SUP>12</SUP> p.o.t./pulse and with a proton beam structure made of four LHC-like extractions, each with a narrow width of ∼3 ns, separated by 524 ns. This very tightly bunched beam allowed a very accurate time-of-flight measurement of neutrinos from CERN to LNGS on an event-by-event basis. The ICARUS T600 detector (CNGS2) has collected 7 beam-associated events, consistent with the CNGS collected neutrino flux of 2.2x10<SUP>16</SUP> p.o.t. and in agreement with the well-known characteristics of neutrino events in the LAr-TPC. The time of flight difference between the speed of light and the arriving neutrino LAr-TPC events has been analysed. The result δt=0.3+/-4.9(stat.)+/-9.0(syst.) ns is compatible with the simultaneous arrival of all events with speed equal to that of light. This is in a striking difference with the reported result of OPERA (OPERA Collaboration, 2011) [1] claiming that high energy neutrinos from CERN arrive at LNGS ∼60 ns earlier than expected from luminal speed.