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Uvod: Sladkorna bolezen zajema več presnovnih motenj z različno etiopatogenezo. Vsem je skupna hiperglikemija, ki je posledica motenega izločanja inzulina in/ali inzulinske rezistence v na inzulin odzivnih tkivih kot so jetra, maščevje in skeletne mišice. Presežek endogenih ali eksogenih glukokortikoidov, kot sta na primer kortizol in deksametazon, lahko vodi v inzulinsko rezistenco, moteno toleranco za glukozo in sladkorno bolezen (t.i. steroidni diabetes). Skeletne mišice so pomembno mesto z inzulinom spodbujenega privzema glukoze in eden izmed najpomembnejših organov, ki jih prizadene inzulinska rezistenca. Farmakološka aktivacija z AMP-aktivirane protein kinaze (AMPK), celičnega energijskega senzorja, v skeletnih mišicah poviša občutljivost na inzulin in s tem pripomore k izboljšanju homeostaze glukoze na ravni celega telesa. Namen: Natančen mehanizem z glukokortikoidi povzročene inzulinske rezistence v skeletnih mišicah ni poznan. Preveriti smo želeli, ali bi k inzulinski rezistenci, ki jo povzročijo glukokortikoidi, lahko prispevala zavora delovanja AMPK. Hipoteze: 1) Kortizol in deksametazon zmanjšata aktivnost inzulinske signalne poti v skeletnomišičnih celicah L6. 2) Kortizol in deksametazon zmanjšata z inzulinom spodbujeni privzem glukoze v skeletnomišičnih celicah L6 kljub povišanju izražanja prenašalcev GLUT1 in GLUT4. 3) Kortizol in deksametazon zmanjšata z A769662 spodbujeno fosforilacijo AMPK in acetil-CoA karboksilaze (ACC) v skeletnomišičnih celicah L6. 4) Kortizol in deksametazon zmanjšata z A769662 spodbujeni privzem glukoze v skeletnomišičnih celicah L6 kljub povišanju izražanja prenašalcev GLUT1 in GLUT4. Metode: Za poskusni model smo uporabili podganje skeletnomišične celice L6. Aktivnost inzulinske signalne poti in AMPK smo ovrednotili s prenosom western, s katerim smo merili fosforilacijo AKT (Thr308 in Ser473), AS160 (Thr642), ERK1/2 (Thr202/Tyr204), ribosomskega proteina S6 (Ser235/236, S6RP), AMPK (Thr172) in ACC (Ser79). Privzem glukoze v skeletnomišične celice L6 smo ocenili z merjenjem privzema 3H-2-deoksiglukoze. Izražanje prenašalcev GLUT1 in GLUT4 smo določili s kvantitativno reakcijo verižne polimeraze v realnem času. Za farmakološko aktivacijo AMPK smo uporabili učinkovino A769662. Rezultati: Kortizol in deksametazonom (0,1 µM in 1 µM) sta v prisotnosti inzulina (12 in 120 nM) povzročila porast fosforilacije AKT (Thr308 in Ser473). V inzulinsko spodbujenih vzorcih kortizol in deksametazon na fosforilacijo AS160 (Thr642) nista vplivala (24-urno tretiranje) oziroma sta jo zmanjšala (72-urno tretiranje). V vzorcih z inzulinom (12 in 120 nM) sta kljub temu povzročila porast privzema glukoze. Fosforilacija ERK1/2 (Thr202/Tyr204) in S6RP (Ser235//236) se je pod vplivom kortizola in deksametazona zmanjšala v prisotnosti inzulina. Izražanje mRNA za prenašalce GLUT1 in GLUT4 se je pod vplivom kortizola in deksametazona povišalo. Kortizol in deksametazon nista spremenila fosforilacije AMPK (Thr172). Z A769662 spodbujena fosforilacija ACC (Ser79) se je ob dodatku kortizola in deksametazona zmanjšala. Kortizol in deksametazon sta v prisotnosti A769662 zvečala privzem glukoze. Zaključek: 1) Kortizol in deksametazon nista zmanjšala aktivnosti inzulinske signalne poti v skeletnomišičnih celicah L6. 2) Kortizol in deksametazon sta zvečala tako izražanje prenašalcev GLUT1 in GLUT4 kot z inzulinom spodbujeni privzem glukoze. 3) Kortizol in deksametazon sta zmanjšala z A769662 spodbujeno fosforilacijo ACC, nista pa vplivala na fosforilacijo AMPK. 4) Kortizol in deksametazon sta zvečala z A769662 spodbujeni privzem glukoze. Introduction: Diabetes mellitus is comprised of several metabolic disorders with different aetiopathogenesis. They are characterized by hyperglycaemia, which results from impaired insulin secretion and/or insulin resistance in insulin-responsive tissues, such as liver, fat and skeletal muscle. Excess endogenous or exogenous glucocorticoids, such as cortisol and dexamethasone, can lead to insulin resistance, impaired glucose tolerance and diabetes mellitus (so-called steroid diabetes). Skeletal muscle is an important site of insulin-stimulated glucose uptake and one of the most important organs affected by insulin resistance. Pharmacological activation of AMP-activated protein kinase (AMPK), a cellular energy sensor, in skeletal muscle increases insulin sensitivity and thus helps to improve glucose homeostasis of the whole body. Aim: The exact mechanism of glucocorticoid induced insulin resistance in skeletal muscle is unknown. The aim of our study was to test whether inhibition of AMPK action could contribute to glucocorticoid-induced insulin resistance. Hypotheses: 1) Cortisol and dexamethasone suppress insulin signalling in L6 skeletal muscle cells. 2) Cortisol and dexamethasone suppress insulin-stimulated glucose uptake in L6 skeletal muscle cells despite an increase in the expression of GLUT1 and GLUT4 transporters. 3) Cortisol and dexamethasone decrease A769662-induced AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in L6 skeletal muscle cells. 4) Cortisol and dexamethasone decrease A769662-stimulated glucose uptake in L6 skeletal muscle cells despite an increase in the expression of GLUT1 and GLUT4 transporters. Methods: The experiments were performed on rat L6 skeletal muscle cells. Insulin signalling pathway and AMPK activity were evaluated by western blotting, which assessed phosphorylation of AKT (Thr308 and Ser473), AS160 (Thr642), ERK1/2 (Thr202 and Tyr204), S6 ribosomal protein (Ser235/236, S6RP), AMPK (Thr172) and ACC (Ser79). The glucose uptake in cultured cells was estimated by 3H-2-deoxyglucose uptake assay. The expression of GLUT1 and GLUT4 transporters was evaluated with real time quantitative polymerase chain reaction. A769662 was used for pharmacological activation of AMPK. Results: In the presence of insulin (12 and 120 nM), cortisol and dexamethasone (0.1 µM and 1 µM) increased the AKT (Thr308 and Ser473) phosphorylation. In insulin stimulated samples, cortisol and dexamethasone did not affect (24-hour treatment) or reduced (72-hour treatment) phosphorylation of AS160 (Thr642), while they increased GLUT1 and GLUT4 mRNA expression and enhanced the insulin-stimulated (12 and 120 nM) glucose uptake. In the presence of insulin, phosphorylation of ERK1/2 (Thr202 and Tyr204) and S6RP (Ser235/236) was reduced by the treatment with glucocorticoids. While cortisol and dexamethasone did not alter the phosphorylation of AMPK (Thr172), they suppressed the A769662-induced phosphorylation of ACC (Ser79) and enhanced the A769662-stimulated glucose uptake. Conclusions: 1) Cortisol and dexamethasone did not decrease the activity of insulin signaling in L6 skeletal muscle cells. 2) Cortisol and dexamethasone increased both the expression of GLUT1 and GLUT4 transporters and insulin-stimulated glucose uptake. 3) Cortisol and dexamethasone diminished A769662-stimulated phosphorylation of ACC but not AMPK. 4) Cortisol and dexamethasone elevated A769662-stimulated glucose uptake.

Cilj ove doktorske je bio da se ispita efekat hipotireoze majke indukovane tokom kasnog graviditeta na endokrini i metabolički status novorođenih teladi tokom prvih sedam dana neonatalnog života. Hipotireoza majke je indukovana davanjem PTU u dozi od 4mg/kg telesne mase tokom poslednjih 20 dana graviditeta. Nakon rađanje, telad koja potiču od majki tretiranih sa PTU (n=10) je svrstano u oglednu grupu, dok je 10 teadi koja su poticala od majki koje nisu tretirane sa PTU svrstano u kontroln grupu. Sva telad su bila odmah po rođenju odvojena od majki i napajana kolostrumu i mlekom tokom ispitivanog perioda. Svakodnevno, tokom prvih sedam dana neonatalnog života teladima je uzimana krv punkcijom v. jugularis. Odmah nakon rođenja teladi uzimani su uzorci tkiva placente majke i tkiva tireoidee teladi. Koncentracija tireoidnih hormona i koncentracija TSH ispitivana je u svim uzetim uzorcima krvi. U uzorcima krvi uzetih 0., 1., 2., 3., 4. i 7. dana nakon rođenja određene su koncentracije glukoze, insulina, kortizola, IGF-I i relativna zastupljenost IGFBP-2 i IGFBP-3. U svim uzorcima krvi uzetih tokom sedam dana ispitivanja, ispitane su koncentracije ukupnih proteina, albumina i globulina, kao i koncentracije holesterola i triglicerida. U uzorcima tkiva placente majki i tkiva tireoidee teladi, ispitivana je ekspresija iRNK za pojedine tipove dejodinaze, dok su u uzorcima tkiva tireoidee određivane i histološke promene. Telad ogledne grupe rađala su se sa značajno nižim koncentracijama tireoidnih hormona (T3 i T4) i značajno višim koncentracijama TSH u odnosu na telad kontrolne grupe. Ova razlika je bila značajna tokom prva dva dana neonatalnog života. Počevši od 3. dana, koncentracije tireoidnih hormona su se kod ogledne grupe povećavale, a TSH snižavale, tako da su koncentracije tireoidnih hormona u periodu od 4. do 6. dana bile značajno više a koncentracije TSH značajno niže kod ogledne nego kod kontrolne grupe. Koncentracije insulina su u momentu rođenja bile značajno niže kod teladi ogledne grupe u odnosu na telad kontrolne grupe. Vrednosti insulinemije su se kod ogledne grupe povećavale tako da je vrednost bila veća nego kod kontrolne grupe već 4. dana, iako ne statistički značajno... The aim of this PhD thesis was to was to examine the effect of induced hypothyroidism in Holstein heifers in the latest stage of pregnancy on endocrine end metabolic status of newborn calves during the first seven days of neonatal life. The study was conducted by inducing hypothyroid state in the dams by oral treatment with 4mg PTU/kg body weight, during a period of 20 days prior to expected calving. After birth, calves originating from dams treated with PTU (n = 10) were classified as experimental group, while 10 calves that originated from dams not treated with PTU were classified as the control group. All calves were separated immediately after birth from their dams and fed colostrum and milk during the test period. During this period, calves body weight was also determined. Blood samples were taken daily by puncture of v. jugularis from each calf for the first seven days of life. Immediately after parturition placental samples and calves thyroid tissue samples were obtained. Concentrations of thyroid hormones and TSH were determined in all blood samples. Concentration of IGF-I and relative presence of IGFBP-2 and IGFBP-3 were determined in samples taken on days 1, 2, 3, 4 and 7 after birth. Concentrations of glucose, insulin and cortisol were determined in samples taken on days 1, 2, 3, 4, 7. Concentrations of total protein, albumin, globulin, triglyceride and cholesterol were determined in samples obtained during the all seven days of study period. On placental and thyroid tissue samples, expression of iRNA for DIO1, DIO2 and DIO3 were determined. Determination of histological changes was done on thyroid tissue samples taken from calves with established macroscopic changes on thyroid gland. Calves in experimental group were born with significantly lower thyroid hormone concentrations and significantly higher TSH concentrations compared to control group. Hypothyroid state was significant within the first two days after birth. After day 3, concentrations of thyroid hormones increased, so in the period of days 4, 5 and 6 they were higher compared to the control group, while the TSH concentrations decreased until day 4 after which the TSH concentrations were lower compared to the control group...

Babesiosis is an emerging tick-transmitted infectious disease of vertebrates that occurs worldwide. In Europe the predominant cause of canine babesiosis is Babesia canis. The disease can be clinically classified into uncomplicated and complicated forms. Both uncomplicated and complicated babesiosis due to Babesia canis appear to be the result of host inflammatory responses. The main aim of this study was to investigate the endocrine anti-inflammatory response in dogs naturally infected with Babesia canis. It was demonstrated that a marked endocrine response occurs in dogs naturally infected with Babesia canis, with significant increases in the concentration of cortisol and insulin. Statistically significant differences were found between the studied groups for all variables (cortisol, insulin and glucose) before the antibabesial treatment. The day after treatment a statistically significant difference was found between healthy dogs and the dogs that survived, as well as the dogs that died, for cortisol and glucose, but not for insulin. In all of the studied dog groups the median value of glucose was within the reference range, but one animal within the group of dogs that survived was hypoglycemic before the antibabesial treatment. After the antibabesial treatment all the studied animals had glucose values within the reference range. A statistically significant positive correlation was found between cortisol and insulin. The results of this study showed that concentrations of cortisol and insulin can be used to predict mortality in canine babesiosis caused by B. canis., Babezioza predstavlja prijeteću zaraznu bolest kralježnjaka koju prenose krpelji, a proširena je diljem svijeta. Glavni uzročnik bolesti u pasa u Europi je vrsta Babesia canis, a bolest se javlja u dva osnovna oblika: nekomplicirana i komplicirana babezioza. Oba oblika su u osnovi posljedica upalnog odgovora nositelja. Glavni je cilj istraživanja bio odrediti endokrini protuupalni odgovor pasa prirodno inficiranih vrstom Babesia canis. Ustanovljen je značajan endokrini protuupalni odgovor, praćen značajnim porastom koncentracije kortizola i inzulina. Utvrđene su statistički značajne razlike među istraživanim skupinama pasa za sve istraživane pokazatelje (kortizol, inzulin i glukoza) prije primjene antibabezijskog lijeka. Dan nakon primjene antibabezijskog lijeka utvrđene su statistički značajne razlike između skupina zdravih pasa, pasa koji su preživjeli babeziozu i pasa koji su uginuli od babezioze za kortizol i glukozu, dok za inzulin nije bilo statistički značajne razlike između navedenih skupina pasa. U svih istraživanih skupina medijan vrijednosti koncentracije glukoze nalazio se unutar referentnog raspona, osim za jednog psa iz skupine koji su preživjeli babeziozu, a koji je bio hipoglikemičan prije primjene antibabezijskog lijeka. U svih istraživanih skupina koncentracija glukoze je bila unutar referentnog raspona dan nakon primjene antibabezijskog lijeka. Utvrđena je statistički značajna pozitivna korelacija između kortizola i inzulina. Rezultati istraživanja su pokazali da se koncentracije kortizola i inzulina mogu koristiti kao pretskazatelji smrtnosti babezioze pasa uzrokovane vrstom Babesia canis.

Metabolic syndrome (MetS) is a chronic, multi-component disease characterised by central obesity, hyperglycaemia, dyslipidaemia, and hypertension. Since MetS leads to type 2 diabetes, cardiovascular disease, development of certain cancers, and eventually to premature death, it is not surprising that it draws the attention of scientists around the world. The aetiopathology of MetS is complex and still not fully understood. This review focuses on the role of endocrine factors such as cortisol and insulin in the development of MetS. It also takes a look at some of the contributing lifestyle and genetic factors as well as at the current knowledge about its treatment., Metabolički sindrom (MetS) kronična je višekomponentna bolest, koju karakteriziraju abdominalna debljina, hiperglikemija, dislipidemija i hipertenzija. Kako MetS dovodi do razvoja šećerne bolesti tipa 2, kardiovaskularnih i nekih malignih bolesti te posljedično do prerane smrti, ne čudi da MetS privlači pozornost znanstvenika diljem svijeta. Etiopatologija MetSa je kompleksna te još nije u potpunosti razjašnjena. Cilj je ovoga rada dati literaturni pregled uloge nekih endokrinih poremećaja, kao što su poremećaj kortizola i inzulina, u razvoju MetSa. Također, razmatrani su i neki faktori načina života/životnog stila te genetički faktori koji pridonose razvoju MetSa. Na kraju su spomenuta trenutačna saznanja u liječenju MetSa i njegovih komponenti.

The aim of this study was to investigate the effect on plasma insulin and cortisol concentrations by feeding Chios ewes with a low energy ration in the late period of gestation. 38 Chios ewes were divided into three groups as pregnant normal energy (PNE), pregnant low energy (PLE) and non pregnant normal energy (N-PNE). Feeding with the treatment rations started on day 105 of the gestation and continued until lambing. Blood samples were obtained on days 120. 127. 134. 141. and 148. during gestation. Plasma insulin concentrations of ewes in the pregnant normal energy were significantly higher than those of the pregnant low energy on days 134 and 141. No significant difference was observed in plasma insulin concentration between pregnant normal energy ewes and non pregnant ewes. Plasma cortisol concentration of ewes in the pregnant low energy was lower on day 120 but higher on day 134 than those of ewes in the pregnant normal energy. As a conclusion an energy intake of greater than 10 MJ/kg ME should be assured for pregnant ewes in the late pregnancy, although energy level of 8.0 MJ/kg ME does not cause a serious energy deficiency., Araştırmanın amacı gebeliğin son dönemindeki enerji yetersizliğinin Sakız ırkı koyunlarda plazma insülin ve kortizol konsantrasyonlarını incelemektir. 38 adet Sakız ırkı koyun normal enerjili gebe grup, yetersiz enerjili gebe grup ve normal enerjili gebe olmayan grup olacak şekilde üç gruba ayrılmışlardır. Gebeliğin 105. gününden doğuma kadar bulundukları gruplara uygun bir şekilde beslenmeye başlanmışlardır. Kan numuneleri gebeliğin 120. 127. 134. 141. ve 148. günlerinde alınmıştır. Normal enerjili gebe koyunların 134. ve 141. günlerindeki plazma insülin konsantrasyonları, yetersiz enerjili gebe gruptakilere göre önemli oranda yüksek çıkmıştır. Normal enerjili gebe gruptaki koyunlar ile normal enerjili gebe olmayan gruptaki koyunların plazma insülin konsantrasyonları arasında bir fark bulunmamıştır. Yetersiz enerjili beslenen gebe koyunlar, normal enerjili beslenen gebelerden gebeliğin 120. gününde daha düşük, 134. gününde ise daha yüksek plazma kortizol konsantrasyonlarına sahip olmuşlardır. Sonuç olarak koyunlar gebeliğin son dönemlerinde 10 MJ/kg ME’den daha yüksek enerji içeren yemlerle beslenmelidir ve gebeliğin son dönemlerinde koyunların 8.0 MJ/kg ME ile beslenmesi ciddi bir enerji eksikliğine yol açmamıştır.

Ispitivana je koncentracija leptina, neuropeptida Y, kortizola, hormona rasta, i insulina u krvi u cirkadijanom ritmu 19 bolesnika liječenih ponavljanim hemodijalizama prije i poslije primjene eritropoetina.Također je ispitivana povezanost leptina s pokazateljima uhranjenosti dijaliziranih bolesnika, te s duljinom i kakvoćom dijalize.