Affiliated to research
2016- Researcher/Group Leader, Karolinska Institutet, Södertälje Hospital.
I am responsible for planning, coordinating, supervising and executing work in the area of cardiometabolic research.
My research focuses on cardiometabolic disease, with a special interest in 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. However, GLP-1 is also produced in neurons of the NTS, which may be of importance for the neuroprotective effects of the peptide.
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.
GLP-1 in the CNS
Recent data published by our research group demonstrates that high fat feeding increases the activation of GLP-1 producing neurons in the NTS, an effect that is partially reduced by drugs regulating glycemia.
GLP-1 and Thoracic aortic aneurysm
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.
GLP-1 in Obesity and Diabetes
Recent data published by our research group demonstrates improved beta cell function and altered postprandial and fasting levels of GLP-1 folowing bariatric surgery in women with NGT.
1. Lietzau G, Ntika S, Pintana H, Tracy LM, Klein T, Nyström T, Darsalia V, Patrone C, Krizhanovskii C. A high-fat diet increases activation of the glucagon-like peptide-1-producing neurons in the nucleus tractus solitarii; an effect that is partially reversed by drugs normalizing glycaemia. Cellular and Molecular Neurobiology
2. Ntika S, Bringman S, Lundquist P, Tracy LM, Krizhanovskii C. Improved beta-cell function and altered plasma levels of GP-1 during OMTT and fasting following bariatric surgery in women with NGT. Intervention in Obesity and Diabetes. 2021;5(1):419-24.
3. Augestad IL, Pintana H, Larsson M, Krizhanovskii C, Nystrom T, Klein T, et al. Regulation of Glycemia in the Recovery Phase After Stroke Counteracts the Detrimental Effect of Obesity-Induced Type 2 Diabetes on Neurological Recovery. Diabetes. 2020;69(9):1961-73.
4. Turpaev K, Krizhanovskii C, Wang X, Sargsyan E, Bergsten P, Welsh N. The protein synthesis inhibitor brusatol normalizes high-fat diet-induced glucose intolerance in male C57BL/6 mice: role of translation factor eIF5A hypusination. FASEB J. 2019;33(3):3510-22.
5. Krizhanovskii C, Franco-Cereceda A. Diabetes, Incretin Therapy and Thoracic Aortic Aneurysm - What Does the Evidence Show? Curr Vasc Pharmacol. 2019;17(5):432-9.
6. Nemme J, Krizhanovskii C, Ntika S, Sabelnikovs O, Vanags I, Hahn RG. Hypervolemia does not cause degradation of the endothelial glycocalyx layer during open hysterectomy performed under sevoflurane or propofol anesthesia. Acta Anaesthesiol Scand. 2019.
7. Hasselgren E, Zdolsek M, Zdolsek JH, Bjorne H, Krizhanovskii C, Ntika S, et al. Long Intravascular Persistence of 20% Albumin in Postoperative Patients. Anesth Analg. 2019.
8. 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):
9. 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.
10. 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
11. 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.
12. 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
13. 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.
14. 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
15. 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
16. 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.
17. 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.
18. 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.
19. 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
20. 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.
21. 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.
22. 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.
23. 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).
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