Hepato-Pancreatic Metabolism
Wednesday 22 April 2009
Room 313BC 13:30-15:30


Daniel T. Boll and Scott Reeder

13:30 468. The Effect of Galactose and Fructose Intake on Synthesis of Liver Glycogen: A 13C-MRS Study
    Roy Jentjens1, Michael Ith2, Eva Scheurer2, Jacques Décombaz3, Asker Jeukendrup4, Chris Boesch2
Nestlé Research Center, Lausanne, Switzerland; 2Dept.Clinical Research, University Bern, Bern, Switzerland; 3Nestlé Research Center, Lausanne, Switzerland; 4School of Sport and Exercise Science, University of Birmingham, Birmingham, UK
    Prolonged, strenuous exercise is associated with liver glycogen depletion (hence hypoglycemia) as well as muscle glycogen depletion. This study investigates the hypothesis that ingestion of large amounts of maltodextrin-based drinks containing added fructose or added galactose results in faster post-exercise liver glycogen synthesis than an iso-osmolar drink with added glucose. In a double blind, randomized cross-over study including 10 well-trained male cyclists, liver glycogen was measured by 13C-MRS. Consumption of the maltodextrin-fructose or -galactose drinks during post-exercise recovery led to significantly higher rates of liver glycogen replenishment over 6 hours than when the iso-osmolar glucose drink was consumed.
13:42 469. 13C MRS Shows Altered Cerebral Glucose Metabolism During Acute Mild Hypoglycemia in Humans
    Kim van de Ven1, Marinette van der Graaf1, Bastiaan de Galan2, Cees Tack2, Arend Heerschap1
Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; 2General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands
    Cerebral glucose metabolism was assessed by 13C-MRS under euglycemic (5.16 mmol/l) or hypoglycemic (2.95 mmol/l) conditions in 8 human volunteers during 2-hour hyperinsulinemic glucose clamps. Using 13C-1-glucose 20% solutions a stable plasma glucose 13C-enrichment was achieved, resulting in high SNR spectra. MRS-measurements were conducted with a 13C/1H volume head coil, and an ISIS-DEPT pulse sequence at 3T. Under hypoglycemic conditions, 13C signals of Asp3 and Glu2 reached a higher level, while Asp2 and Glu3 (and also Glu4) reached a lower level compared to euglycemic conditions This indicates altered cerebral glucose metabolism during mild hypoglycemia, possibly reflecting upregulated anaplerosis.
13:54 470. Effect of Suppression of Free Fatty Acids on ATP Turnover and Inorganic Phosphate Uptake in Type 2 Diabetes Studied by 31P-MRS During an Isoglycaemic-Hyperinsulinaemic Clamp
    Kieren Grant Hollingsworth1, Ee Lin Lim1, Mei Jun Chen1, Jean Gerrard1, Roy Taylor1
Newcastle Magnetic Resonance Centre, Newcastle University, Newcastle, Tyne and Wear, UK
    7 patients (age 56.7±4.3) with well-controlled Type 2 diabetes were brought in fasted on two separate study days and given (i) acipimox and (ii) a placebo tablet. Saturation transfer between ATP and Pi was used to measure ATP turnover 3 hours and just before a 120 minute isoglycaemic-hyperinsulinaemic clamp. Further measurements were made 20 minutes and 90 minutes into the clamp. Acipimox suppressed free fatty acids rapidly. The ATP flux at 90 minutes on the acipimox study day was significantly greater than with placebo. The percentage increase in inorganic phosphate was significantly greater at 90 minutes with acipimox.
14:06 471. Endogenous Gluconeogenic Sources Account for the Majority of Hepatic Glycogen Synthesis After an Oral Glucose Load in 24-Hour Fasted Rats
    Ana Francisca Soares1,2, John Griffith Jones1, Francisco Veiga2, Rui Albuquerque Carvalho1
Biochemistry and Center for Neurosciences and Cell Biology, University of Coimbra, Coimbra, Portugal; 2Pharmaceutical Technology, University of Coimbra, Coimbra, Portugal
    Hepatic glycogen fluxes were characterized in 24-hour fasted rats following an oral tracer-enriched load. Combination of 13C isotopomer analysis with 2H-enrichment from 2H2O, resolved load contribution from that of endogenous gluconeogenesis to hepatic glycogen. The latter accounted for 66 ± 13 % of the glycogen synthesized during the experiment whereas less than one third originated in the oral load following direct and indirect pathways at similar extents: 18 ± 3 % and 16 ± 2 %, respectively. Thus hepatic glycogen synthesis contributes to normoglygemia mostly by diverting gluconeogenic carbons from hepatic glucose production rather than through net uptake of glucose.
14:18 472. Localized MRS of Human Pancreas
    Ildiko Lingvay1, Angela L. Price1, Jaime Legendre1, Sarmistha Sen1, Lidia S. Szczepaniak2
Internal Medicine, University of Texas, Southwestern Medical Center, Dallas, TX, USA; 2Internal Medicine & Radiology, University of Texas, southwestern Medical Center, Dallas, TX, USA
    Obesity is known to influence insulin sensitivity, but its direct effect on insulin secretion is still debated. The lipotoxicity hypothesis provides a unifying link between chronic positive energy balance and metabolic syndrome abnormalities. Accumulation of fat in the human liver, skeletal muscle, and the heart, along with associated decline in the function of these organs, has been confirmed by previous clinical studies, yet data on fat accumulation in the human pancreas is limited to autopsy reports, and there is very limited information regarding the relationship between insulin secretion and pancreatic fat accumulation. We performed studies in humans to determine whether proton-localized magnetic resonance spectroscopy can be used to noninvasively assess pancreatic steatosis. We performed a series of studies in healthy human volunteers to document the reproducibility of the pancreatic triglyceride measurement in vivo and examined the cross-sectional relationship between pancreatic triglyceride content, body mass index, and glycemic status.
14:30 473. The Effect of Nutritional Early-Life Programming on Adult Body Composition and Appetite Regulation
    Jelena Anastasovska1, Nachiket Abhay Nadkarni1, Po-Wah So2, Neena Modi3, Elizabeth Louise Thomas1, Gary Frost4, Jimmy D. Bell1
Metabolic and Molecular Imaging Group, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK; 2Biological Imaging Centre, Imaging Sciences Department, MRC Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, UK; 3Section of Neonatal Medicine, Chelsea and Westminster Campus, Imperial College London, London, UK; 4Nutrition and Dietetics Research Group, Metabolic Medicine, Hammersmith Hospital, Imperial College London, London, UK
    The effect of nutrition at specific stages of development has been investigated using different diets during fetal and neonatal growth. In this study, we investigate the effects of low protein diet during either pregnancy or lactation in combination with a hypercaloric post-lactation diet, on lipid content and distribution and appetite regulation, in the adult offspring using MRI and MRS. We show that the stage of early life at which undernutrition occurs has significant effects in determining the adult phenotype. Low protein in the early post-natal period leads to an improvement in adiposity and lipid metabolism, despite an increased appetite.
14:42 474. Phosphorous and Carbon Spectroscopy of Porcine Islet Extracts : Comparison of Effects of Normoxic and Hypoxic Culture Conditions
    Chardonay Julia Vance1,2, Hitoshi Kubo3, Kristen Stewart Maynard1, Klearchos K. Papas1, Gulin Oz2
Diabetes Institute, U of MN, Minneapolis, MN, USA; 2CMRR, U of MN, Minneapolis, MN, USA; 3Medical Imaging, University of Tokushima Graduate School, Tokushima, Japan
    Pancreatic islet transplantation is a promising treatment for restoring normoglycemia in some patients with Type-1 diabetes. Islet death induced by hypoxia limits viable islet yield and the success rate of transplantations. To address the metabolic consequences of islet exposure to anoxia, we compared anaerobic and oxidative carbohydrate metabolism (as measured by 13C label incorporation from 13C-glucose to metabolites in exchange with TCA cycle intermediates) and energy status (as measured by ATP-to-ADP ratio via 31P NMR) of highly purified porcine islets. The ATP/ADP ratio fell during anoxia. GABA, lactate and alanine synthesis from glucose increased, and glutamate synthesis decreased during anoxia.
14:54 475. Liver 31P MRSI Using an 8-Channel Dual-Tuned 31P/1H Coil at 3T
    Anshuman Panda1,2, Judy Rose James1,2, Uwe Boettcher3, Rahul Srinivasa Raghavan1, Kumar Sandrasegaran2, Alex Aisen2, Helmut Stark4, Navin Bansal1,2, Ulrike Dydak1,2
School of Health Sciences, Purdue University, West Lafayette, IN, USA; 2Department of Radiology, Indiana University School of Medicine, Indianapolis, IN, USA; 3Siemens Healthcare, Erlangen, Germany; 4Stark Contrast MRI Coils Research, Erlangen, Germany
    In-vivo results of 31P MR Spectroscopic Imaging (MRSI) of a whole axial slice through the liver obtained from a novel eight-channel phased-array dual-tuned 31P/1H coil at 3T are presented in this work. Data was acquired using a slice-selective MRSI sequence, showing that this coil allows MRSI of a whole slice of the abdomen and provides good sensitivity throughout the liver. The signal to noise ratio of the spectra allows for relative phase correction before signal combination from each channel. A nominal resolution of 25x25x30 mm3 over a field-of-view of 400x250x30 mm3 can be achieved within a scantime of ~20 min.
15:06 476.

Toward Quantitation of Pancreatic β Cell Mass Using a Two-Site Exchange Analysis of Manganese-Enhanced MR Images

    Patrick F. Antkowiak1, Moriel H. Vandsburger1, Sarah Tersey2, Raghavendra G. Mirmira2, Frederick H. Epstein1,3
Biomedical Engineering, University of Virginia, Charlottesville, VA, USA; 2Medicine, Indiana University; 3Radiology, University of Virginia
    In normal individuals, pancreatic beta cells release insulin into the bloodstream after an increase in blood glucose level. In Type 1 diabetes, beta cell mass and function are impaired. Manganese (Mn) enhanced MRI has been used to probe beta cell function; we aimed to extract parameters related to beta cell mass using a two site exchange analysis of Mn-enhanced MR images. Two site exchange analysis revealed that diabetic mice had increased intra- and extracellular compartment T1 values and had a decreased intracellular fraction, consistent with the loss of beta cell mess, as compared to non-diabetic mice.
15:18 477. MR-Guided Engraftment of Human Pancreatic Islet Cells in a Diabetic Swine Using Immunoprotection with Clinically Applicable Magnetocapsules
    Dian Respati Arifin1,2, Aravind Arepally1, Thomas W. Link2,3, Wesley D. Gilson1,4, Victor A. Ferrari5, Robert L. Wilensky5, Dara L. Kraitchman1, Jeff W.M. Bulte1,2
Radiology and Radiological Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA; 2Cellular Imaging Section, Institute for Cell Engineering, Johns Hopkins University School of Medicine; 3Biomedical Engineering, Johns Hopkins University School of Medicine; 4Siemens Corporate Research, Inc., Baltimore, MD, USA; 5Cardiovascular Division, Hospital of University of Pennsylvania, Philadelphia, PA, USA
    Transplantation of pancreatic cells is a promising treatment of type 1 diabetes. Pancreatic cells were immunoprotected inside novel alginate/protamine sulfate/alginate magnetocapsules. Magneto-encapsulated human pancreatic cells transplanted in a streptozotocin-induced diabetic swine were viable and functional for at least 14 days post-transplantation. The swine was vetsulin-independent and showed healthy blood glucose levels 2 days and one day post-transplantation, respectively. Magnetocapsules were clearly visualized as hypointensities in vivo using a 1.5T clinical MR-scanner. Magneto-encapsulated pancreatic cells show potential for treatment of type 1 diabetes in a large animal model, providing a means to non-invasively monitor cell transplantation in real-time using MR-imaging.