Tina Tičinović Kurir

Expression of calcium/calmodulin-dependent protein kinase II and pain-related behavior in rat models of type 1 and type 2 diabetes

BACKGROUND:Abnormalities in peripheral nerves and dorsal root ganglia are noticed in the early stage of experimentally provoked diabetic neuropathy. Enzyme calcium/calmodulin-dependent protein kinase II (CaMKII) may have a modulating role in diabetic neuropathy because of its role in calcium homeostasis. METHODS:A model of type 1 diabetes mellitus (DM1) was induced with 55 mg/kg of the streptozotocin and for DM2 induction a combination of high-fat diet and low-dose streptozotocin (35 mg/kg) was used. Pain-related behavior was analyzed using thermal and mechanical stimuli. Two weeks and 2 months after induction of diabetes rats were euthanized, and the expression of CaMKII and its isoforms in the dorsal root ganglia were analyzed using immunofluorescence. RESULTS:Both types of diabetes were successfully induced, as confirmed by hyperglycemia. Increased pain-related behavior became evident in DM1 rats in 2 weeks after diabetes induction, but not in DM2 rats. The expression of total CaMKII and the phosphorylated &agr; isoform of CaMKII increased in DM1 animals concurrently with pain-related behavior. Expression of &agr;, &bgr;, &ggr;, and &dgr; isoforms in DM1 animals and expression of total CaMKII and all of its analyzed isoforms in DM2 animals remained unchanged. CONCLUSIONS:Our findings may indicate involvement of CaMKII in transmission of nociceptive input early in DM1, but not in DM2. CaMKII may be a suitable pharmacological target for diabetic neuropathy.

The Missing Link - Likely Pathogenetic Role of GM3 and Other Gangliosides in the Development of Diabetic Nephropathy

Despite scientific advances, diabetic nephropathy remains both a therapeutical challenge, and one of the major diabetic complications. Chemical structure of gangliosides, the most complex of glycosphingolipids, is characterised by one or more sialic acids and carbohydrate groups linked to a ceramide structure. Their potential pathogenetic role in a number of disorders linked to diabetes mellitus has recently been conjectured, due to evidence of their negative modulation of the insulin-mediated signaling and general effects on key cell functions like proliferation, differentiation, apoptosis, cellular signaling and adhesion. Elevated levels of advanced glycation products (AGE) usually found in diabetic conditions seem to be responsible for increased concentration of a-series gangliosides in tissues, most notably GM3. GM3 was shown to compromise the renal pericyte and mesangial cell regeneration via the inactivation of VEGF receptor and the receptor-associated Akt signaling pathway. Likewise, the lipid raft theory opened a new research area for GM3 influence, since in the glycosynapse model glycosphingolipids have a key cell-to-cell communication unit with modulating capabilities on signaling receptors. The goal of this review is to provide insight into currently available theories on proposed mechanisms that mark the GM3 as a pathophysiological mediator in the development of diabetic nephropathy.

Acute Renal Failure Associated with Rhabdomyolysis in Acute Q Fever

The clinical presentation of Q fever is polymorphic and non-specific, and it may be presented as an acute or chronic disease. Renal complications of acute Q fever such as acute glomerulonephritis are not uncommon. Acute renal failure induced by rhabdomyolysis in acute Q fever has until now never been reported in the literature. We presented a case of acute Q fever associated by extreme rhabdomyolysis and consecutive acute renal failure. A male patient was treated with doxycycline and continuous venovenous hemodiafiltration. After two weeks of treatment, the patient completely recovered kidney function, and there were no clinical abnormalities. Acute Q fever must be considered as a possible cause of rhabdomyolysis and acute renal failure. The continuous venovenous hemodiafiltration may be effective, and it seems to be the treatment of choice in severe rhabdomyolysis and consecutive acute renal failure.

Ganglioside GM3 content in skeletal muscles is increased in type 2 but decreased in type 1 diabetes rat models: implications of glycosphingolipid metabolism in pathophysiology of diabetes

Ganglioside GM3 is found in the plasma membrane, where its accumulation attenuates insulin receptor signaling. Considering the role of skeletal muscles in insulin‐stimulated glucose uptake, the aim of the present study was to determine the expression of GM3 and its precursors in skeletal muscles of rat models of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively).

Health-related quality of life in type 2 diabetes mellitus patients with different risk for obstructive sleep apnea

Purpose Our study primarily aimed to investigate health-related quality of life (HRQoL) in type 2 diabetes mellitus (T2DM) patients with different risk for obstructive sleep apnea (OSA). Patients and methods This cross-sectional, questionnaire-based study included 466 adult patients with T2DM on regular visit to Center for Diabetes of University Hospital of Split from April to September 2017. All subjects underwent detailed anamnestical evaluation and physical examination with anthropometric measurements. Additionally, all subjects completed STOP (Snoring, Tiredness, Observed apnea, and high blood Pressure) questionnaire to assess risk for OSA, Epworth Sleepiness Scale to assess daytime sleepiness, and Medical Outcomes Study Short Form-36 (SF-36) instrument to evaluate HRQoL. Results Most subjects (N=312, 67.0%) represented high-risk OSA group based on STOP questionnaire (STOP score ≥2). Statistically significantly lower HRQoL scores in all SF-36 dimensions were found in T2DM patients with high risk for OSA compared to low-risk group (P<0.001). STOP score showed statistically significant negative correlation with all SF-36 dimensions (P<0.001). In multiple linear regression analysis, STOP score was confirmed as statistically significant independent predictor for all SF-36 components, adjusted for body mass index, age, glycated hemoglobin, and T2DM duration (P<0.001). Conclusion Our study found that high proportion of patients with T2DM are at high risk for OSA. Furthermore, we showed that group of T2DM patients with high risk for OSA has lower HRQoL in all SF-36 dimensions compared to low-risk patients.

Adropin and Inflammation Biomarker Levels in Male Patients With Obstructive Sleep Apnea: A Link With Glucose Metabolism and Sleep Parameters

STUDY OBJECTIVES The main objectives of the study were to determine plasma adropin, systemic inflammation biomarker levels, and glucose metabolism parameters in patients with moderate and severe obstructive sleep apnea (OSA) compared to healthy controls. METHODS In this study, we included 50 male patients with OSA (25 moderate and 25 severe) and 25 age- and sex-matched control subjects. All subjects underwent fasting sampling of peripheral blood for laboratory analyses. RESULTS Adropin plasma levels were significantly lower in the severe OSA group in comparison with the moderate and control groups (4.50 ± 1.45 versus 6.55 ± 1.68 versus 8.15 ± 1.79 ng/mL, P < .001). Plasma biomarkers of systemic inflammation were significantly increased in patients with moderate OSA (interleukin [IL]-6 and tumor necrosis factor alpha [TNF-α]) and severe OSA (IL-6, TNF-α, high-sensitivity C-reactive protein) when compared with controls (P < .001). Adropin levels showed a significant negative correlation with IL-6 (r = -.419, P < .001), TNF-α (r = -.540, P < .001), fasting glucose (r = -.331, P = .004), hemoglobin A1c (r = -.438, P < .001), homeostatic model assessment insulin resistance index (r = -.213, P = .046), and polysomnographic parameters including apnea-hypopnea index (r = -.615, P < .001) and oxygen desaturation index (r = -.573, P < .001). A multivariate regression analysis showed that plasma adropin remained as a significant negative predictor of severe OSA status, when adjusted for age and body mass index and computed along with other inflammatory biomarkers in the regression model (odds ratio 0.069, 95% confidence interval 0.009-0.517, P = .009). CONCLUSIONS Plasma adropin concentrations significantly correlate with indices of disease severity in patients with OSA, suggesting that adropin potentially plays an important role in the complex pathophysiology of the disease.