The Diabetes Screen provides an array of standardized procedures, scientific expertise, and state-of-the-art technologies for characterization of in vivo glucose homeostasis, insulin action, pancreatic β-cell function, tissue-specific pathophysiological and anatomical alterations in mouse models. Key to investigating a multifaceted syndrome such as diabetes and its complications are close interactions between the Diabetes and the other GMC Screens. The Diabetes Screen is not included in the Primary GMC Screen and represents a Secondary or Tertiary Screen for phenotyping mouse models with regards to a potential diabetes phenotype.
Aims of the GMC Diabetes Screen are to
· link murine pathophysiology to human disease,
· better understand diabetes and its complications,
· identify new mechanisms and therapeutic targets, and
· test novel treatment options
- Plasma insulin concentrations (ELISA)
- Intraperitoneal Insulin Tolerance Test (i.p.ITT): crude in vivo test for whole body insulin sensitivity
- Euglycemic-hyperinsulinemic clamp: in vivo test for whole-body and organ specific insulin sensitivity
- Hyperglycemic clamp: in vivo test for pancreatic β-cell function
- Morphological islet characterisation (Immunohistochemistry)
- Organ lipid quantification (biochemical lipid extraction and subsequent enzymatic triacylglycerol determination, immunohistochemistry)
- Insulin signaling in tissue (Western blot analysis, e.g. tissue Akt and pAkt)
- Compound challenge tests (administration via oral, intravenous, subcutaneous, intraabdominal route)
- Diet challenge tests (to induce general obesity or non-alcoholic fatty liver associated hepatic insulin resistance)
References (selected publications)
2. Zhang D, Christianson J, Liu ZX, Tian L, Choi CS, Neschen S, Dong J, Wood PA, Shulman GI. 2010. Resistance to high-fat diet-induced obesity and insulin resistance in mice with very long-chain acyl-CoA dehydrogenase deficiency. Cell Metab. 11(5):402-11.
3. Neschen S, Katterle Y, Richter J, Augustin R, Scherneck S, Mirhashemi F, Schürmann A, Joost HG, Klaus S. 2008. Uncoupling protein 1 expression in murine skeletal muscle increases AMPK activation, glucose turnover, and insulin sensitivity in vivo. Physiol Genomics. 33(3):333-40.
4. Danial NN, Walensky LD, Zhang CY, Choi CS, Fisher JK, Molina AJ, Datta SR, Pitter KL, Bird GH, Wikstrom JD, Deeney JT, Robertson K, Morash J, Kulkarni A, Neschen S, Kim S, Greenberg ME, Corkey BE, Shirihai OS, Shulman GI, Lowell BB, Korsmeyer SJ. 2008. Dual role of proapoptotic BAD in insulin secretion and beta cell survival. Nat Med. 14(2):144-53.
5. Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI. 2007. n-3 Fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-alpha-dependent manner. Diabetes. 56(4):1034-41.
6. Neschen S, Morino K, Hammond LE, Zhang D, Liu ZX, Romanelli AJ, Cline GW, Pongratz RL, Zhang XM, Choi CS, Coleman RA, Shulman GI. 2005. Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice. Cell Metab. 2(1):55-65.