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Camilla Krizhanovskii

Camilla Krizhanovskii
Södertälje Hospital, Karolinska Institutet · Dept of Research, Affiliated researcher at Karolinska Institutet Department of Clinical Science and Education Södersjukhuset

Associate Professor, Ph.D.

About

36
Publications
4,352
Reads
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Citations
Introduction
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.
Additional affiliations
November 2015 - present
Karolinska Institutet, Södertälje Sjukhus
Position
  • Head of Department
June 2013 - November 2015
Uppsala University
Position
  • PostDoc Position
January 2013 - June 2013
Karolinska Institutet
Position
  • PostDoc Position

Publications

Publications (36)
Article
Full-text available
Glucagon-like peptide-1 (GLP-1) regulates processes involved in the pathophysiology of thoracic aortic aneurysms (TAAs), including inflammation, while protecting against aortic aneurysms in animal models. Type 2 diabetes (T2D) involves altered GLP-1 signaling due to pathology and/or therapy and is associated with reduced prevalence of TAAs. We aime...
Article
Full-text available
Aims/hypothesis ZBED6 (zinc finger, BED-type containing 6) is known to regulate muscle mass by suppression of Igf2 gene transcription. In insulin-producing cell lines, ZBED6 maintains proliferative capacity at the expense of differentiation and beta cell function. The aim was to study the impact of Zbed6 knockout on beta cell function and glucose t...
Article
Background: The endothelial glycocalyx, a carbohydrate-rich layer coating all endothelial surfaces, plays a fundamental role in the function of microcirculation. The primary aim of this study was to evaluate the feasibility of using dexamethasone and albumin to protect the endothelial glycocalyx in patients undergoing abdominal surgery. Secondary...
Article
Full-text available
A reduced prevalence of a thoracic aortic aneurysm (thoracic AA) is observed in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1)/GLP-1-based anti-diabetic therapy has indicated protective effects in thoracic AA and regulates the processes controlling the vascular tissue expression of Syndecan-1 (Sdc-1). Sdc-1 expression on macrophages infiltr...
Article
Full-text available
Glucagon-like peptide-1 (GLP-1) is a peripheral incretin and centrally active peptide produced in the intestine and nucleus tractus solitarii (NTS), respectively. GLP-1 not only regulates metabolism but also improves cognition and is neuroprotective. While intestinal GLP-1-producing cells have been well characterized, less is known about GLP-1-prod...
Preprint
Full-text available
Glucagon-like peptide-1 (GLP-1) is a peripheral incretin and centrally active peptide produced in the intestine and nucleus tractus solitarii (NTS), respectively. GLP-1 not only regulates metabolism but also improves cognition and is neuroprotective. While intestinal GLP-1-producing cells have been well characterized, less is known about GLP-1-prod...
Article
Background: Preclinical experiments show that an inflammatory reaction causes degradation of the endothelial glycocalyx layer and accelerated capillary leakage of albumin and fluid. The hypothesis in the present study was that elevated plasma concentrations of glycocalyx degradation products are associated with greater capillary leakage in humans....
Article
The interplay between obesity and T2D in post-stroke recovery is unclear. Moreover, the impact of glucose control during the chronic phase after stroke is undetermined.We investigated whether obesity-induced T2D impairs neurological recovery after stroke by using a clinically relevant experimental design. We also investigated the potential efficacy...
Article
Full-text available
Background: Fluid-induced hypervolemia may stimulate the release of natriuretic peptides and cause degradation (shedding) of the endothelial glycocalyx layer. Sevoflurane is believed to protect the glycocalyx, but the importance of using sevoflurane to prevent shedding during routine surgery is unclear. Methods: The plasma concentrations of brai...
Article
Background: Albumin may persist intravascularly for a shorter time in patients after major surgery than in healthy volunteers due to a surgery-induced breakdown (shedding) of the endothelial glycocalyx layer. Methods: In this nonrandomized clinical trial, an IV infusion of 3 mL/kg of 20% albumin was given at a constant rate during 30 minutes to...
Article
Background Fatty acids (FAs), and especially monounsaturated FAs (MUFAs) stimulate GLP-1 release. However, lipotoxicity is indicated in GLP-1 secreting cells following long-term exposure to elevated levels of saturated FAs (SFAs) in vivo and in vitro, where in vitro studies indicate that cosupplementation with MUFAs confers lipoprotection. SFAs and...
Article
The naturally occurring quassinoid compound brusatol improves the survival of insulin-producing cells when exposed to the proinflammatory cytokines IL-1β and IFN-γ in vitro. The aim of the present study was to investigate whether brusatol also promotes beneficial effects in mice fed a high-fat diet (HFD), and if so, to study the mechanisms by which...
Article
Epidemiological evidence supports reduced prevalence of thoracic aortic aneurysm (TAA) in diabetes. The mechanisms underlying this negative association are unknown. Some studies support that hyperglycemia has effects on the extracellular matrix, resulting in collagen cross-links and altered proteolytic activity, which ultimately counteracts aneurys...
Article
Full-text available
Background Diabetes is a risk factor for peripheral, coronary, and cerebrovascular disease. In contrast, results also indicate that patients with diabetes have reduced prevalence of aortic aneurysms, although the mechanisms remain largely unknown. We hypothesize that altered endogenous secretion of the intestinal hormone glucagon-like peptide-1 (GL...
Article
Full-text available
Background: Enhanced IAPP production may contribute to islet amyloid formation in type 2 diabetes. The objective of this study was to determine the effects of the saturated fatty acid palmitate on IAPP levels in human β-cells. Methods: EndoC-βH1 cells and human islets were cultured in the presence of sodium palmitate. Effects on IAPP/insulin mRNA e...
Article
Full-text available
Background Surgery with and without hypervolaemia may cause shedding (breakdown) of the endothelial glycocalyx layer, but the severity of this problem is unclear. Methods In this preliminary report of a larger clinical trial, the plasma and urine concentrations of three biomarkers of glycocalyx shedding (syndecan-1, hyaluronic acid and heparan sulf...
Article
Full-text available
Fatty acids acutely stimulate GLP-1 secretion from L-cells in vivo. However, a high fat diet has been shown to reduce the density of L-cells in the mouse intestine and a positive correlation has been indicated between L-cell number and GLP-1 secretion. Thus, the mechanism of fatty acid-stimulated GLP-1 secretion, potential effects of long-term expo...
Article
Aims - Human pancreatic islets are known to die in response to the free fatty acid of sodium palmitate when cultured in vitro. This is in contrast to EndoC-βH1 cells, which in our hands are not sensitive to the cell death-inducing effects sodium palmitate, making these cells seemingly unsuitable for lipotoxicity studies. However, the EndoC-βH1 cell...
Article
Full-text available
Objective Renal conservation (retention) of fluid might affect the outcome of hospital care and can be indicated by increased urinary concentrations of metabolic waste products. We obtained a reference material for further studies by exploring the prevalence of fluid retention in a healthy population. Methods Spot urine sampling was performed in 3...
Data
Raw data used for the calculations. English Version. (XLS)
Data
Measured parameters depending on gender. (DOCX)
Data
Raw data used for the calculations. Original. (XLS)
Article
Evidence indicates that subtle abnormalities in glucocorticoid (GC) plasma concentrations and/or in tissue sensitivity to GCs are important in the metabolic syndrome, and it is generally agreed that GCs induce insulin resistance. In addition, it was recently reported that short-term exposure to GCs reduced the insulinotropic effects of the incretin...
Article
Full-text available
Elevated serum free fatty acids (FFAs) contribute to the pathogenesis of type-2-diabetes (T2D), and lipotoxicity is observed in many cell types. We recently showed that simulated hyperlipidemia induces lipoapoptosis also in GLP-1-secreting L-cells in vitro, while metformin confers lipoprotection. The aim of this study was to determine if a high fat...
Article
Full-text available
Glucagon-like peptide-1 (GLP-1), secreted from gut L-cells upon nutrient intake, forms the basis for novel drugs against type 2 diabetes (T2D). Secretion of GLP-1 has been suggested to be impaired in T2D and in conditions associated with hyperlipidemia and insulin resistance. Further, recent studies support lipotoxicity of GLP-1-producing cells in...
Article
Full-text available
Background Type 2 diabetes (T2D) is a strong risk factor for developing neurodegenerative pathologies. T2D patients have a deficiency in the intestinal incretin hormone GLP-1, which has been shown to exert neuroprotective and anti-inflammatory properties in the brain. Methods Here we investigate potential sources of GLP-1 in the CNS and the effect...
Article
Background: Evidence is emerging that elevated serum free fatty acids (hyperlipidemia) contribute to the pathogenesis of type-2-diabetes, and lipotoxicity is observed in many cell types. We recently published data indicating lipotoxic effects of simulated hyperlipidemia also in GLP-1-secreting cells, where the antidiabetic drug metformin conferred...
Article
Background: Metformin is the most frequently prescribed drug for treatment of type 2 diabetes. It improves insulin resistance and glycemia by reducing hepatic gluconeogenesis. In addition, diabetic patients on metformin therapy have elevated levels of the insulinotropic hormone glucagon-like peptide-1 (GLP-1) and metformin has been shown to regula...
Article
Liraglutide, an analog of glucagon-like peptide-1 (GLP-1), is an effective anti-diabetic agent with few side effects. Since native GLP-1 exerts vascular effects, we investigated changes in pancreatic islet blood flow using a non-radioactive microsphere technique, as well as insulin concentration and glucose tolerance after 17 day treatment with lir...
Article
Full-text available
Diabetes is a strong risk factor for premature and severe stroke. The GLP-1R (glucagon-like peptide-1 receptor) agonist Ex-4 (exendin-4) is a drug for the treatment of T2D (Type 2 diabetes) that may also have neuroprotective effects. The aim of the present study was to determine the efficacy of Ex-4 against stroke in diabetes by using a diabetic an...

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Projects

Projects (3)
Project
To elucidate CNS expression/secretion of the antidiabetic, anti-obesogenic and neuroprotective peptide Glucagon like peptide-1 (GLP-1), to ultimately contribute to developing tools to modulate CNS GLP-1 signaling for therapeutic benefit.
Project
To identify the signaling mechanisms regulating function and viability of GLP-1 secreting L-cells, and the influence of a diabetic milieu