Diabetes & Fat Metabolism

Friday 16 May 2014

Mangesh Kulkarni^1,2, Dian Arifin^1,2, and Jeff Bulte^1,2
1Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, Maryland, United States, ²Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, Baltimore, Maryland, United States

Transplantation of microencapsulated islets circumvents the need for immunosuppression which is a requirement for the clinically used Edmonton protocol. We developed complementary strategies to improve transplant survival. Incorporation of perfluorocarbons within the capsules enabled in vivo monitoring using 19F MRI following subcutaneous implantation of human islets in a mouse model of type I diabetes mellitus. In this xenogeneic environment, encapsulated human islet viability was significantly improved following co-transplantation with encapsulated human MSCs.

Lin Z. Li^1,2, Stephen Kadlececk¹, Hoora Shaghaghi¹, He N. Xu^1,2, Harrilla Profka¹, and Rahim Rizi^1
1Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, United States, ²Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, University of Pennsylvania, Philadelphia, Pennsylvania, United States

Abnormal enzyme activities and cellular redox state have been observed in various medical conditions including cancer, diabetes, neurodegenerative diseases and lung diseases. We employed hyperpolarized 13C-pyruvate NMR to investigate non-invasively how the enzyme kinetics (rate constants) and cellular redox state may be modulated by the levels of metabolites. Our results indicate a strong coupling of the lactate dehydrogenase reaction with the cellular redox state. Hyperpolarized 13C-pyruvate can be a metabolic indicator of redox state for the study of normal physiology and diseases.

JanakiRaman Rangarajan^1,2, Ting Yin^3,4, Josephine Gilbert⁵, Ashwini Atre^3,4, Anna Eriksson⁵, Tom Dresselaers^3,4, Frederik Maes¹, Ulf Ahlgren⁵, and Uwe Himmelreich^3,4
1ESAT/PSI - Medical Image Computing, KU Leuven, Leuven, Belgium, ²iMinds-KU Leuven Future Health Department, KU Leuven, Leuven, Belgium,³Biomedical MRI unit, Department of Imaging and Pathology, KU Leuven, Belgium, ⁴Molecular Small Animal Imaging Center (MoSAIC), KU Leuven, Belgium, ⁵Umeå Centre for Molecular Medicine, Umea University, Sweden

Islet graft transplantation is an promising treatment practice for diabetic treatment, but progressive islet loss is a major issue, which drives the interest to study islet location and function in vivo. MRI offers high spatial resolution for in vivo assessment of pancreatic islets (PI) labeled with iron-oxide particles, but the quantification of PIs in MR is confounded by the false positive signals. Optical projection tomography (OPT) offers multi-spectral assessment of PI labeled with fluorescent markers, but only allow ex vivo measurements. Using spatial normalization methods, we co-register the multi-modal data of MRI and OPT, which allowed co-localization of PIs. The. successful co-registration of pancreatic tissue allowed cross-validation of PIs in MR images, confirming its suitability for in vivo PI imaging. This is an essential prerequisite for future validation of in vivo MRI data using beta-cell targeting iron oxide based nanoparticles

Dian Liu¹, Jelena Curcic^1,2, Andreas Steingoetter^1,2, and Sebastian Kozerke^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zurich, Switzerland, ²Division of Gastroenterology and Hepatology, University of Zurich, Zurich, Switzerland

The increase in nutrition-related diseases has prompted immense efforts to understand how food systems, and in particular lipids, are sensed, processed and digested in the gastrointestinal (GI) tract. Accurate in vivo fat quantification by MRI requires modeling of all relevant chemical shift species contained in fat, and thus the acquisition of sufficient number of echo times. Objective of this work was to validate and implement hierarchical IDEAL for measuring intragastric fat distribution of lipid emulsions. Using a 6-point IDEAL approach, intragastric distribution and emptying of fat in emulsions could be assessed within a single breath hold.

Lydia Le Page¹, Oliver Rider², Andrew Lewis², Lucia Giles¹, Vicky Ball¹, Latt Mansor¹, Lisa Heather¹, and Damian Tyler^1
1Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom, ²Oxford Centre for Clinical Magnetic Resonance Research, Oxford, United Kingdom

Diabetics have reduced systemic glucose metabolism, partly due to reduced pyruvate dehydrogenase (PDH) flux, which leads to high blood glucose levels. Dichloroacetate (DCA) stimulates PDH and this study investigated its in vivo effect on the diabetic heart and liver. Four weeks of DCA treatment in diabetic rats normalised blood glucose levels, restored cardiac PDH flux and elevated hepatic PDH flux compared to controls. Diastolic dysfunction, observed in the diabetic heart, was not present in diabetic rats treated with DCA. We conclude that PDH modulation may be a suitable treatment for the metabolic and functional abnormalities seen in the diabetic heart.

Ekkehard Küstermann¹, Anke Meyer², Katharina Stolz², Wolfgang Dreher¹, and Kathrin Maedler^2
1AG "in-vivo-MR", FB2, Universität Bremen, Bremen, Bremen, Germany, ²Center for Biomolecular Interactions Bremen, Universität Bremen, Bremen, Germany

Diabetes research and therapy will benefit from non-invasive methods of analyzing pancreatic beta-cell mass (BCM) and activity. Manganese mediated MR imaging is a very potent tool for non-invasive measurements of pancreatic activity. The Mn-induced signal time course of pancreatic tissue is analyzed with a mathematical model consisting of three sequentially ordered compartments: a source and two pancreatic compartments. The pancreatic MR-signal can be modeled by (i) a small compartment with similar signal changes as in the liver and (ii) a larger compartment characterized by a much slower signal change.

Jae Mo Park¹, Sonal Josan¹, Ralph Hurd², James Graham³, Peter Havel³, David Bendahan⁴, Dirk Mayer⁵, Daniel Spielman¹, and Thomas Jue^6
1Radiology, Stanford University, Stanford, CA, United States, ²GE Healthcare, Menlo Park, CA, United States, ³Molecular Bioscience, UC Davis, Davis, CA, United States, ⁴Centre de Resonance Magnetique Biologique et Medicale, Marseille, France, ⁵Diagnostic Radiology and Nuclear Medicine, University of Maryland, MD, United States, ⁶Biochemistry, UC Davis, Davis, CA, United States

We performed in vivo experiments to assess the oxidative pathway contribution in the type 2 diabete mellitus (T2DM) model using hyperpolarized [1-13C]lactate and [2-13C]pyruvate. The metabolism of hyperpolarized [1-13C]lactate in the muscle was different in T2DM as compared to control rats, in particular with respect to PDH activity. The restoration of PDH activity with dichloroacetate in the T2DM rat suggests a non-negligible contribution of oxidative metabolism impairment in diabetes and a potential role for PDH activation to restore glucose homeostasis. [2-13C]pyruvate experiment suggests that ketogenesis is more active rather than the oxidative phosphorylation in diabetic muscle metabolism after dichloroacetate infusion.

Fiona Elizabeth Smith¹, Mavin Macauley¹, Peter Thelwall¹, and Roy Taylor^1
1Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Skeletal muscle plays a major role in glucose homeostasis in normal health. Approximately 30% of meal carbohydrate is stored as muscle glycogen after the first meal of the day and rises after subsequent meals. Liver stores approximately 20% of meal carbohydrate in healthy subjects. Glycogen depots behave as a dynamic buffer allowing rapid storage of osmotically active glucose. However, the effectiveness of this diurnal mechanism has not been previously studied in Type 2 diabetes. The study aim was to quantify changes in skeletal muscle and liver glycogen concentration during normal eating in Type 2 Diabetes comparing this to healthy subjects.

Hussein Srour¹, Anna Ulyanova¹, and kai Hsiang chuang^1
1Singapore Bioimaging Consortium, Singapore, Singapore

Manganese-enhanced MRI (MEMRI) is a useful method for measuring calcium-dependent cellular activity due to accumulation of Mn2+ in cells via voltage-gated calcium channels. We investigated the feasibility of MEMRI as a method to detect BAT activation in mice induced by cold exposure. We show for the first time that MEMRI can differentiate between BAT and WAT tissue in mice.

Inès ABDESSELAM^1,2, Bénédicte GABORIT^2,3, Frank KOBER¹, Alexis JACQUIER⁴, Olivier EMUNGANIA⁵, Marie-Christine ALESSI², Monique BERNARD¹, and Anne DUTOUR^2,3
1Faculté de médecine, Aix-Marseille University, CRMBM, CNRS7339, Marseille, France, ²Faculté de médecine, Aix-Marseille University, NORT, Inserm1062/Inra1260, Marseille, France, ³Endocrinology, Metabolic diseases and nutrition, CHU Nord, Marseille, France, ⁴Radiology, CHU TImone, Marseille, France, ⁵Gastroenterology, CHU Nord, Marseille, France

Bariatric surgery (BS) reduce, after 6 months, epicardial fat deposition but doesn't induce any change in myocardial triglyceride content. The aim of this study was to investigate the impact of BS on pancreatic fat content, to determine whether we can reduce myocardial triglyceride content two years after BS and whether decreased level of triglyceride content 6 months after BS could be maintained 2 years later. For that purpose, we used 1H-MRS. Our study provides compelling evidences that pancreatic fat increase with type 2 diabetes and could be decreased with BS. Finally, we show that this decrease is maintained overtime.