Annette Schurmann

Animal models in diabetes research

Part I: Rodent Models of Type 1 Diabetes 1. The Non-Obese Diabetic (NOD) Mouse as a Model of Human Type 1 Diabetes Kritika Kachapati, David Adams, Kyle Bednar, and William M. Ridgway 2. Assessment of Diabetic Nephropathy in the Akita Mouse Jae-Hyung Chang and Susan B. Gurley 3. The BB Rat as a Model of Human Type 1 Diabetes Rita Bortell and Chaoxing Yang Part II: Rodent Models of Type 2 Diabetes 4. Diabetes in Mice with Monogenic Obesity: The db/db Mouse and Its Use in the Study of Cardiac Consequences Darrell D. Belke and David L. Severson 5. Pathophysiology and Genetics of Obesity and Diabetes in the New Zealand Obese Mouse: A Model of the Human Metabolic Syndrome Reinhart Kluge, Stephan Scherneck, Annette Schurmann, and Hans-Georg Joost 6. The TALLYHO Mouse as a Model of Human Type 2 Diabetes Jung Han Kim and Arnold M. Saxton 7. Diet-Induced Diabetes in the Sand Rat (Psammomys obesus) Nurit Kaiser, Erol Cerasi, and Gil Leibowitz 8. Diabetes in Zucker Diabetic Fatty Rat Masakazu Shiota and Richard L. Printz 9. The GK Rat: A Prototype for the Study of Non-Overweight Type 2 Diabetes? Bernard Portha, Marie-Helene Giroix, Cecile Tourrel-Cuzin, Herve Le-Stunff, and Jamileh Movassat 10. Experimentally Induced Rodent Models of Type 2 Diabetes Md. Shahidul Islam and Rachel Dorothy Wilson Part III: Other Species 11. Investigation and Treatment of Type 2 Diabetes in Nonhuman Primates Barbara C. Hansen Part IV: General Methodology 12. Determination of Beta-Cell Function: Insulin Secretion of Isolated Islets Michael Willenborg, Kirstin Schumacher, and Ingo Rustenbeck 13. Determination of Beta-Cell Function: Ion Channel Function in Beta Cells Martina Dufer 14. Measurement of Glucose Homeostasis In Vivo: Glucose and Insulin Tolerance Tests Francesco Beguinot and Cecilia Nigro 15. Measurement of Glucose Homeostasis In Vivo: Combination of Tracers and Clamp Techniques Masakazu Shiota 16. Measurement of Insulin Sensitivity in Skeletal Muscle In Vitro Henrike Sell, Jorgen Jensen, and Juergen Eckel 17. Beta-Cell Autoimmunity Yannick F. Fuchs, Kerstin Adler, and Ezio Bonifacio 18. Positional Cloning of Diabetes Genes Gudrun A. Brockmann and Christina Neuschl 19. Retinal Digest Preparation: A Method to Study Diabetic Retinopathy Nadine Dietrich and Hans-Peter Hammes 20. Lineage Tracing of Pancreatic Stem Cells and Beta Cell Regeneration Isabelle Houbracken, Iris Mathijs, and Luc Bouwens 21. Genetic Lineage Tracing of Beta Cell Neogenesis Iris Mathijs, Isabelle Houbracken, and Luc Bouwens Rita Bortell and Chaoxing Yang

Arf-Like Proteins

At least 10 different proteins have homology to members of the Arf family but each lacks activities that define “true” Arfs. In addition, the percent identity between these 10 proteins, when aligned with Arfs or to each other, is lower (typically 40–60%) than that between Arfs (greater than 65% identity). A summary of current information on each is presented below. Despite extensive conservation of structure between Arfs and Arls, the Arls represent a much more functionally divergent collection of GTPases, with apparent roles in vesicle traffic (Arl1, Sarl), microtubule organization (Arl2, Arl3), spermatogenesis (Arl4), and differentiation (Arfrp1). However, the overlap in binding partners between functionally distinct Arls suggests that Arfs and Arls are likely to have a complex web of overlapping and distinct functions.

A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes

Abstract To explore the genetic determinants of obesity and Type 2 diabetes (T2D), the German Center for Diabetes Research (DZD) conducted crossbreedings of the obese and diabetes-prone New Zealand Obese mouse strain with four different lean strains (B6, DBA, C3H, 129P2) that vary in their susceptibility to develop T2D. Genome-wide linkage analyses localized more than 290 quantitative trait loci (QTL) for obesity, 190 QTL for diabetes-related traits and 100 QTL for plasma metabolites in the outcross populations. A computational framework was developed that allowed to refine critical regions and to nominate a small number of candidate genes by integrating reciprocal haplotype mapping and transcriptome data. The efficiency of the complex procedure was demonstrated for one obesity QTL. The genomic interval of 35 Mb with 502 annotated candidate genes was narrowed down to six candidates. Accordingly, congenic mice retained the obesity phenotype owing to an interval that contains three of the six candidate genes. Among these the phospholipase PLA2G4A exhibited an elevated expression in adipose tissue of obese human subjects and is therefore a critical regulator of the obesity locus. Together, our broad and complex approach demonstrates that combined- and comparative-cross analysis exhibits improved mapping resolution and represents a valid tool for the identification of disease genes.

Loss of periostin occurs in aging adipose tissue of mice and its genetic ablation impairs adipose tissue lipid metabolism

Remodeling of the extracellular matrix is a key component of the metabolic adaptations of adipose tissue in response to dietary and physiological challenges. Disruption of its integrity is a well‐known aspect of adipose tissue dysfunction, for instance, during aging and obesity. Adipocyte regeneration from a tissue‐resident pool of mesenchymal stem cells is part of normal tissue homeostasis. Among the pathophysiological consequences of adipogenic stem cell aging, characteristic changes in the secretory phenotype, which includes matrix‐modifying proteins, have been described. Here, we show that the expression of the matricellular protein periostin, a component of the extracellular matrix produced and secreted by adipose tissue‐resident interstitial cells, is markedly decreased in aged brown and white adipose tissue depots. Using a mouse model, we demonstrate that the adaptation of adipose tissue to adrenergic stimulation and high‐fat diet feeding is impaired in animals with systemic ablation of the gene encoding for periostin. Our data suggest that loss of periostin attenuates lipid metabolism in adipose tissue, thus recapitulating one aspect of age‐related metabolic dysfunction. In human white adipose tissue, periostin expression showed an unexpected positive correlation with age of study participants. This correlation, however, was no longer evident after adjusting for BMI or plasma lipid and liver function biomarkers. These findings taken together suggest that age‐related alterations of the adipose tissue extracellular matrix may contribute to the development of metabolic disease by negatively affecting nutrient homeostasis.