Om mig
2016- Researcher/Group Leader, Karolinska Institutet, Södertälje Hospital.
I am responsible for planning, coordinating, supervising and executing work in the area of diabetes research.
Forskningsbeskrivning
Diabetes Research
My research focuses largely on central and peripheral effects of GLP-1, and the regulation of GLP-1 secretion in health and diabetes.
GLP-1 is secreted from intestinal L-cells in response to food intake and stimulates insulin secretion in a glucose dependent manner, while also inhibiting glucagon secretion, reducing appetite and exerting cardioprotective and neuroprotective effects.
GLP-1 based therapy (incretin therapy) is successfully used in the treatment of Type 2 Diabetes (T2D). Ongoing clinical trials also evaluate incretin therapy in subjects with obesity without T2D, as well as in cardiovascular and neurodegenerative disorders. Studies indicate that reduced GLP-1 plasma levels come as a result of diabetes disease progression, and are also associated with increased BMI and insulin resistance independent of T2D. The future of incretin therapy is to understand the mechanisms behind the altered GLP-1 secretion in diabetes in order to learn how to preserve/potentiate endogenous secretion, as well as to identify novel patient groups that may benefit from incretin therapy.
Recent data published by our research group show that the plasma levels of GLP-1 are altered in patients with thoracic aortic aneurysm. Studies designed to identify a potential role for GLP-1 in aneurysm formation are currently ongoing.
Our research group has also shown that saturated fatty acids and simulated diabetic hyperlipidemia induce apoptotic cell death of GLP-1 secreting cells, while unsaturated fatty acids confer lipoprotection, and in a mouse model of insulin resistance a reduced number of intestinal L-cells is indicated.
Publications
1. Nemme J, Hahn RG, Krizhanovskii C, Ntika S, Sabelnikovs O, Vanags I. Minimal shedding of the glycocalyx layer during abdominal hysterectomy. BMC Anesthesiol. 2017;17(1):
2. Thombare K, Ntika S, Wang X, Krizhanovskii C. Long chain saturated and unsaturated fatty acids exert opposing effects on viability and function of GLP-1-producing cells: Mechanisms of lipotoxicity. PLoS One. 2017;12(5):e0177605.
3. Krizhanovskii C, Ntika S, Olsson C, Eriksson P, Franco-Cereceda A (2017) Elevated circulating fasting glucagon-like peptide-1 in surgical patients with aortic valve disease and diabetes. Diabetol Metab Syndr 9: 79
4. Krizhanovskii C., Elksnis A., Wang X., Gavali H., Kristinsson H., Bergsten P., Scharfmann R., Welsh N. EndoC-βH1 cells display increased sensitivity to sodium palmitate when cultured in DMEM/F12 medium. Islets. 2017;9(3):e1296995.
5. Krizhanovskii C, Fred RG, Oskarsson ME, Westermark GT, Welsh N (2017) Addition of exogenous sodium palmitate increases the IAPP/insulin mRNA ratio via GPR40 in human EndoC-betaH1 cells. Ups J Med Sci 122: 149-159
6. Kuhre, R.E., Holst J.J, and Kappe C. The regulation of function, growth and survival of GLP-1-producing L-cells. Clin Sci (Lond), 2016. 130(2): p. 79-91.
7. Hahn RG, Grankvist N, Krizhanovskii C. Urinary Analysis of Fluid Retention in the General Population: A Cross-Sectional Study. PLoS One. 2016;11(10):e0164152
8. Fred, R.G., Kappe C., Ameur A., Cen J., Bergsten P., Ravassard P., Scharfmann R., Welsh N. Role of the AMP kinase in cytokine-induced human EndoC-betaH1 cell death. Mol Cell Endocrinol, 2015. 414: p. 53-63
9. Kappe C., Fransson L., Wolbert P., Ortsäter H. Glucocorticoids suppress GLP-1 secretion: possible contribution to their diabetogenic effects. Clin Sci (Lond), 2015. 129(5): p. 405-14.
10. Kappe, C., Holst, J.J., Zhang, Q., Sjöholm, Å. Regulation of GLP-1-producing cells in vivo: Effects of high-fat diet and the anti-diabetic drug metformin. Diabetol Metab Syndr. 2014;6:70.
11. Kappe, C., Holst, J.J., Zhang, Q., Sjöholm, Å. Evidence for paracrine/autocrine regulation of GLP-1-producing cells. Am J Physiol Cell Physiol. 2013 Aug 28.
12. Darsalia, S. Mansouri, H. Ortsater, A. Olverling, N. Nozadze, C. Kappe, K. Iverfeldt, L.M. Tracy, N. Grankvist, A. Sjoholm, C. Patrone, Glucagon-like peptide-1 receptor activation reduces ischaemic brain damage following stroke in Type 2 diabetic rats, Clin Sci (Lond) 122 (2012) 473-483
13. Wu, A. Olverling, L. Fransson, H. Ortsater, C. Kappe, X. Gao, A. Sjoholm, Early intervention with liraglutide improves glucose tolerance without affecting islet microcirculation in young Goto- Kakizaki rats, Regul Pept 177 (2012) 92-96.
14. Kappe, C. Tracy, L.M. Patrone, C. Iverfeldt, K. Sjoholm, A. GLP-1 secretion by microglial cells and decreased CNS expression in obesity, J Neuroinflammation 9 (2012) 276.
15. Kappe, C. Holst, J.J. Zhang, Q. Sjoholm, A. Molecular mechanisms of lipoapoptosis and metformin protection in GLP-1secreting cells. Biochem Biophys Res Commun 2012; 427:91-95.
16. Kappe , C. Patrone, J.J. Holst, Q. Zhang, A. Sjoholm, Metformin protects against lipoapoptosis and enhances GLP-1 secretion from GLP-1-producing cells, J Gastroenterol (2012).
Utbildning
2018 Ass. Professor (Docent) in Medical Cell Biology, Uppsala University
2017 Web course for supervisors, Karolinska Institutet
2016 Academic Teacher Training Course, Uppsala University
2014 Doctoral Supervision Course, Karolinska Institutet
2014 Course in Problem based learning – case studies in small groups. Uppsala University
2013 PhD in Medicine, Karolinska Institutet.
2010 Laboratory Animal Science certificate, Karolinska Institutet
2007 M.Sc. Molecular Biology, Stockholm University / CSU Hayward, CA USA
2002 Minor in Business Administration, CSU Hayward, CA USA