Impairments in endoplasmic reticulum (ER) Ca2+ homeostasis have been linked to β cell dysfunction... more Impairments in endoplasmic reticulum (ER) Ca2+ homeostasis have been linked to β cell dysfunction and diabetes development; however, the pathways mediating these effects are not fully understood. Store-operated Ca2+ entry (SOCE) replenishes ER Ca2+ levels through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). We found that female, but not male, mice with β cell-specific STIM1 deletion (STIM1Δβ) had reduced β cell mass, increased α cell mass, and reduced expression of markers of β cell identity. To determine the mechanisms underlying this sexually dimorphic phenotype, RNA sequencing, immunofluorescent staining, and Ca2+ imaging experiments were performed using islets from control and STIM1Δβ mice and WT and STIM1 KO INS-1 cells. RNA sequencing of islets from STIM1Δβ mice identified 55 pathways that were significantly modulated (P<0.05), including “estrogen receptor signaling”, “mitochondrial dysfunction”, and “endocytosis”, and “estrogen receptor signaling”. Consistent with a role for SOCE in mitochondrial function, STIM1 KO cells decreased mitochondrial Ca2+ levels. Furthermore, we used the novel fluorescent time construct, syncollin-dsRedE5TIMER, to demonstrate an abnormal accumulation of aged insulin granules in STIM1 KO cells. Lastly, to test the relationship between STIM1 expression and glucose regulation in humans, we queried a publicly available NCBI GEO dataset derived from organ donors with and without type 2 diabetes (T2D). In this dataset, islet STIM1 expression was negatively correlated with HbA1c levels in female organ donors (n=35, r=-0.38, p=0.035), while there was no correlation in male donors. Together, these data highlight a novel role for STIM1 in the maintenance of mitochondrial function and insulin granule turnover. These findings confirm the importance of Ca2+ regulation within the β cell and highlight the significant role of sex as a biological variable in diabetes pathogenesis. Disclosure T.Kono: None. M.Slak rupnik: None. P.Krishnan: None. P.Sohn: None. M.Mclaughlin: None. W.Wu: None. S.Postic: None. P.Krishnan: None. C.Lee: None. M.Slak rupnik: None. C.Evans-molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics, Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics, Research Support; Lilly, Astellas Pharma Inc. Funding National Institutes of Health (R01DK093954, R01DK127236, U01DK127786, R01DK127308, UC4DK104166); U.S. Department of Veterans Affairs (I01BX001733)
Presented with sensory challenges, living cells employ extensive noisy, fluctuating signaling and... more Presented with sensory challenges, living cells employ extensive noisy, fluctuating signaling and communication among themselves to compute a physiologically proper response. Using coupled stochastic oscillators model, we propose that biological computation mechanism undertaken by insulin secreting beta-cells consists of a combination of dual intracellular Ca2+ release processes to ensure multilayered exploration contributing to enhanced robustness and sensitivity. The computational output is macroscopically observed as disorder-order phase transition in a collective beta-cell response to increases in nutrient concentrations. Our own experimental data and analogies from previously described examples of biological computation suggest that the initial limited response to nutrients may be followed by an adaptive phase to expand the sensory spectrum and consolidate memory.
The mechanisms accounting for the functional changes of α- and β-cells over the course of Type... more The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity...
DEAD-kutija RNA helikaza DDX5 uključena je u brojne stanične procese kroz metabolizam RNA ili kao... more DEAD-kutija RNA helikaza DDX5 uključena je u brojne stanične procese kroz metabolizam RNA ili kao koregulator raznih transkripcijskih faktora. U ovom radu istražen je utjecaj proteina DDX5 u signalnom putu NF-кB i staničnom ciklusu. Kako bismo dobili stanice HeLa bez ekspresije DDX5 ili s delecijom C-terminalnog kraja DDX5 proteina koji sadrži proteinsku domenu Pfam za koju se smatra da je odgovorna za aktivaciju puta NFκB, korištena je metoda delecije pomoću plazmida CRISPR/Cas9. Delecija gena DDX5 bila je letalna za stanice. Stanice HeLa s delecijom dijela sekvence DDX5, HeLa DDX5ΔPfam bile su vijabilne, ali su također pokazivale smanjenu stopu umnožavanja. Usporedno su metodom unosa antisens RNA za DDX5 uzgojene stanice HeLa i primarne stanice HUVEC sa utišanom ekspresijom DDX5, te se istražio utjecaj ove promjene na NF-κB aktivaciju i stanični ciklus.The DEAD-box RNA helicase DDX5 is included in all sort of cellular processes through its ability to metabolize RNA or as a co-regu...
From the perspective of the lab exercises leader and teaching assistant for the Bioremediation co... more From the perspective of the lab exercises leader and teaching assistant for the Bioremediation course, it was very difficult to design and conduct a set of exercises that would fit the course curriculum and satisfactorily demonstrate bioremediation basics through practical laboratory work. Thus, Bioremediation course students designed the experiment with the help of the teaching assistant; a simulation of possible bioremediation of “Jarun” lake in Zagreb, Croatia, if contaminated with cationic surfactant. The experiment nicely showed how natural bioremediation differs from engineered bioremediation and the levels of success between different types of engineered bioremediation. The laboratory exercises were designed to be interesting and the results perceivable to the students. Editor's Note: The ASM advocates that students must successfully demonstrate the ability to explain and practice safe laboratory techniques. For more information, read the laboratory safety section of the ...
Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover im... more Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca2+ concentration ([Ca2+]c). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells. Here we report the effect of physiological adrenaline levels on [Ca2+]c dynamics in beta cell collectives in mice pancreatic tissue slice preparation. We used confocal microscopy with a high spatial and temporal resolution to evaluate glucose-stimulated [Ca2+]c events and their sensitivity to adrenaline. We investigated glucose concentrations from 8-20 mM to assess the concentration of adrena...
Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function... more Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function. To explain this effect, a number of mechanisms was proposed involving both extracellular and intracellular targets and pathways. Here, we focus on reassessing the influence of extracellular pH on glucose-dependent beta cell activation and collective activity in physiological conditions. To this end we employed mouse pancreatic tissue slices to perform high-temporally resolved functional imaging of cytosolic Ca2+ oscillations. We investigated the effect of either physiological H+ excess or depletion on the activation properties as well as on the collective activity of beta cell in an islet. Our results indicate that lowered pH invokes activation of a subset of beta cells in substimulatory glucose concentrations, enhances the average activity of beta cells, and alters the beta cell network properties in an islet. The enhanced average activity of beta cells was determined indirectly utili...
Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene ele... more Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene elektrone u atomskim orbitalama. Kisikovi radikali su najbitnija vrsta slobodnih radikala koja nastaje unutar živih bića. ROS i RNS poznati su po svojoj dvostrukoj ulozi u stanici. Jedna od uloga slobodnih radikala je da uzrokuju oksidativni stres. Organizmi su razvili različit mehanizme obrane od oksidativnog stresa. Jedan od mehanizama je i obrana enzimima oksidativnog stresa. Slobodni radikali sudjeluju i u mnogim normalnim fiziološkim procesima kao što su: redoks regulirana produkcija NO, ROS proizvodnja pomoću fagocitozne NAD(P)H oksidaze, ROS produkcija pomoću NAD(P)H oksidaze u nefagocitoznim stanicama, produkcija ROS-a kao posljedica promjene koncentracije kisika, redoks regulacija stanične adhezije, redoks regulacija imunološkog odgovora i apoptoza inducirana ROS-om. Oksidativni stres je pronađen i u različitim fiziološkim stanjima bolesti kao što su: kardiovaskularne bolesti, tumo...
U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog područja. Mjerenjem morfoloških značajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim značajkama ukazano je na morfološke razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je ključ za razlikovanje i određivanje ovih morfološki vrlo sličnih vrsta, čime bi se nadopunili opisi u postojećim europskim ključevima za trčkeThere are four species of the subgenus Eucarabus in Croatia: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi and Carabus (Eucara...
U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog područja. Mjerenjem morfoloških značajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim značajkama ukazano je na morfološke razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je ključ za razlikovanje i određivanje ovih morfološki vrlo sličnih vrsta, čime bi se nadopunili opisi u postojećim europskim ključevima za trčkeThere are four species of the subgenus Eucarabus in Croatia: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi and Carabus (Eucara...
U Hrvatskoj postoje cetiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje cetiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog podrucja. Mjerenjem morfoloskih znacajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim znacajkama ukazano je na morfoloske razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je kljuc za razlikovanje i određivanje ovih morfoloski vrlo slicnih vrsta, cime bi se nadopunili opisi u postojecim europskim kljucevima za trcke
DEAD-kutija RNA helikaza DDX5 ukljucena je u brojne stanicne procese kroz metabolizam RNA ili kao... more DEAD-kutija RNA helikaza DDX5 ukljucena je u brojne stanicne procese kroz metabolizam RNA ili kao koregulator raznih transkripcijskih faktora. U ovo
Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support... more Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The supraphysiological ACh concentration further increases the oscillation...
Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene ele... more Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene elektrone u atomskim orbitalama. Kisikovi radikali su najbitnija vrsta slobodnih radikala koja nastaje unutar živih bica. ROS i RNS poznati su po svojoj dvostrukoj ulozi u stanici. Jedna od uloga slobodnih radikala je da uzrokuju oksidativni stres. Organizmi su razvili razlicit mehanizme obrane od oksidativnog stresa. Jedan od mehanizama je i obrana enzimima oksidativnog stresa. Slobodni radikali sudjeluju i u mnogim normalnim fizioloskim procesima kao sto su: redoks regulirana produkcija NO, ROS proizvodnja pomocu fagocitozne NAD(P)H oksidaze, ROS produkcija pomocu NAD(P)H oksidaze u nefagocitoznim stanicama, produkcija ROS-a kao posljedica promjene koncentracije kisika, redoks regulacija stanicne adhezije, redoks regulacija imunoloskog odgovora i apoptoza inducirana ROS-om. Oksidativni stres je pronađen i u razlicitim fizioloskim stanjima bolesti kao sto su: kardiovaskularne bolesti, tumo...
ObjectiveInsulin release from pancreatic beta cells is driven by cytosolic [Ca2+]c oscillations o... more ObjectiveInsulin release from pancreatic beta cells is driven by cytosolic [Ca2+]c oscillations of several different time scales that are primarily attributed to plasma membrane ion channel activity. However, the majority of past studies have been performed at supraphysiological glucose concentrations above 10 mM using electrophysiologic approaches that solely measure plasma membrane ion fluxes. The role of endoplasmic reticulum (ER) Ca2+ stores in glucose-stimulated Ca2+ signaling remains poorly understood.MethodsIn this study, we hypothesized new, brighter [Ca2+]c sensors coupled with high-resolution functional Ca2+ imaging could be used to test a previously unappreciated role for the ryanodine and IP3 intracellular Ca2+ release channels in [Ca2+]c oscillations stimulated by increases from 6 mM to 8 mM glucose.ResultsUsing mouse pancreas tissue slices exposed to physiological glucose increments, our results show that glucose-dependent activation of IP3 and ryanodine receptors prod...
Impairments in endoplasmic reticulum (ER) Ca2+ homeostasis have been linked to β cell dysfunction... more Impairments in endoplasmic reticulum (ER) Ca2+ homeostasis have been linked to β cell dysfunction and diabetes development; however, the pathways mediating these effects are not fully understood. Store-operated Ca2+ entry (SOCE) replenishes ER Ca2+ levels through reversible gating of plasma membrane Ca2+ channels by the ER Ca2+ sensor, stromal interaction molecule 1 (STIM1). We found that female, but not male, mice with β cell-specific STIM1 deletion (STIM1Δβ) had reduced β cell mass, increased α cell mass, and reduced expression of markers of β cell identity. To determine the mechanisms underlying this sexually dimorphic phenotype, RNA sequencing, immunofluorescent staining, and Ca2+ imaging experiments were performed using islets from control and STIM1Δβ mice and WT and STIM1 KO INS-1 cells. RNA sequencing of islets from STIM1Δβ mice identified 55 pathways that were significantly modulated (P<0.05), including “estrogen receptor signaling”, “mitochondrial dysfunction”, and “endocytosis”, and “estrogen receptor signaling”. Consistent with a role for SOCE in mitochondrial function, STIM1 KO cells decreased mitochondrial Ca2+ levels. Furthermore, we used the novel fluorescent time construct, syncollin-dsRedE5TIMER, to demonstrate an abnormal accumulation of aged insulin granules in STIM1 KO cells. Lastly, to test the relationship between STIM1 expression and glucose regulation in humans, we queried a publicly available NCBI GEO dataset derived from organ donors with and without type 2 diabetes (T2D). In this dataset, islet STIM1 expression was negatively correlated with HbA1c levels in female organ donors (n=35, r=-0.38, p=0.035), while there was no correlation in male donors. Together, these data highlight a novel role for STIM1 in the maintenance of mitochondrial function and insulin granule turnover. These findings confirm the importance of Ca2+ regulation within the β cell and highlight the significant role of sex as a biological variable in diabetes pathogenesis. Disclosure T.Kono: None. M.Slak rupnik: None. P.Krishnan: None. P.Sohn: None. M.Mclaughlin: None. W.Wu: None. S.Postic: None. P.Krishnan: None. C.Lee: None. M.Slak rupnik: None. C.Evans-molina: Advisory Panel; Provention Bio, Inc., DiogenX, Avotres Inc., Neurodon, MaiCell Therapeutics, Other Relationship; Isla Technology, Bristol-Myers Squibb Company, Nimbus Therapeutics, Research Support; Lilly, Astellas Pharma Inc. Funding National Institutes of Health (R01DK093954, R01DK127236, U01DK127786, R01DK127308, UC4DK104166); U.S. Department of Veterans Affairs (I01BX001733)
Presented with sensory challenges, living cells employ extensive noisy, fluctuating signaling and... more Presented with sensory challenges, living cells employ extensive noisy, fluctuating signaling and communication among themselves to compute a physiologically proper response. Using coupled stochastic oscillators model, we propose that biological computation mechanism undertaken by insulin secreting beta-cells consists of a combination of dual intracellular Ca2+ release processes to ensure multilayered exploration contributing to enhanced robustness and sensitivity. The computational output is macroscopically observed as disorder-order phase transition in a collective beta-cell response to increases in nutrient concentrations. Our own experimental data and analogies from previously described examples of biological computation suggest that the initial limited response to nutrients may be followed by an adaptive phase to expand the sensory spectrum and consolidate memory.
The mechanisms accounting for the functional changes of α- and β-cells over the course of Type... more The mechanisms accounting for the functional changes of α- and β-cells over the course of Type 1 Diabetes (T1D) development are largely unknown. Permitted by our established technology of high spatiotemporal resolution imaging of cytosolic Ca2+ ([Ca2+]c) dynamics on fresh pancreas tissue slices, we tracked the [Ca2+]c dynamic changes, as the assessment of function, in islet α- and β-cells of female non-obese diabetic (NOD) mice along the development of spontaneous diabetes. We showed that during the phases of islet inflammation, 8 mM glucose-induced synchronized short [Ca2+]c events in β-cells were diminished, whereas long [Ca2+]c events were gradually more triggerable at sub-stimulatory 4 and 6 mM glucose. In the islet destruction phase, the synchronized short [Ca2+]c events in a subset of β-cells resumed at high glucose condition, while the long [Ca2+]c events were significantly elevated already at sub-stimulatory glucose concentrations. In the α-cells, the glucose sensitivity...
DEAD-kutija RNA helikaza DDX5 uključena je u brojne stanične procese kroz metabolizam RNA ili kao... more DEAD-kutija RNA helikaza DDX5 uključena je u brojne stanične procese kroz metabolizam RNA ili kao koregulator raznih transkripcijskih faktora. U ovom radu istražen je utjecaj proteina DDX5 u signalnom putu NF-кB i staničnom ciklusu. Kako bismo dobili stanice HeLa bez ekspresije DDX5 ili s delecijom C-terminalnog kraja DDX5 proteina koji sadrži proteinsku domenu Pfam za koju se smatra da je odgovorna za aktivaciju puta NFκB, korištena je metoda delecije pomoću plazmida CRISPR/Cas9. Delecija gena DDX5 bila je letalna za stanice. Stanice HeLa s delecijom dijela sekvence DDX5, HeLa DDX5ΔPfam bile su vijabilne, ali su također pokazivale smanjenu stopu umnožavanja. Usporedno su metodom unosa antisens RNA za DDX5 uzgojene stanice HeLa i primarne stanice HUVEC sa utišanom ekspresijom DDX5, te se istražio utjecaj ove promjene na NF-κB aktivaciju i stanični ciklus.The DEAD-box RNA helicase DDX5 is included in all sort of cellular processes through its ability to metabolize RNA or as a co-regu...
From the perspective of the lab exercises leader and teaching assistant for the Bioremediation co... more From the perspective of the lab exercises leader and teaching assistant for the Bioremediation course, it was very difficult to design and conduct a set of exercises that would fit the course curriculum and satisfactorily demonstrate bioremediation basics through practical laboratory work. Thus, Bioremediation course students designed the experiment with the help of the teaching assistant; a simulation of possible bioremediation of “Jarun” lake in Zagreb, Croatia, if contaminated with cationic surfactant. The experiment nicely showed how natural bioremediation differs from engineered bioremediation and the levels of success between different types of engineered bioremediation. The laboratory exercises were designed to be interesting and the results perceivable to the students. Editor's Note: The ASM advocates that students must successfully demonstrate the ability to explain and practice safe laboratory techniques. For more information, read the laboratory safety section of the ...
Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover im... more Adrenaline inhibits insulin secretion from pancreatic beta cells to allow an organism to cover immediate energy needs by unlocking internal nutrient reserves. The stimulation of α2-adrenergic receptors on the plasma membrane of beta cells reduces their excitability and insulin secretion mostly through diminished cAMP production and downstream desensitization of late step(s) of exocytotic machinery to cytosolic Ca2+ concentration ([Ca2+]c). In most studies unphysiologically high adrenaline concentrations have been used to evaluate the role of adrenergic stimulation in pancreatic endocrine cells. Here we report the effect of physiological adrenaline levels on [Ca2+]c dynamics in beta cell collectives in mice pancreatic tissue slice preparation. We used confocal microscopy with a high spatial and temporal resolution to evaluate glucose-stimulated [Ca2+]c events and their sensitivity to adrenaline. We investigated glucose concentrations from 8-20 mM to assess the concentration of adrena...
Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function... more Extracellular pH has the potential to affect various aspects of the pancreatic beta cell function. To explain this effect, a number of mechanisms was proposed involving both extracellular and intracellular targets and pathways. Here, we focus on reassessing the influence of extracellular pH on glucose-dependent beta cell activation and collective activity in physiological conditions. To this end we employed mouse pancreatic tissue slices to perform high-temporally resolved functional imaging of cytosolic Ca2+ oscillations. We investigated the effect of either physiological H+ excess or depletion on the activation properties as well as on the collective activity of beta cell in an islet. Our results indicate that lowered pH invokes activation of a subset of beta cells in substimulatory glucose concentrations, enhances the average activity of beta cells, and alters the beta cell network properties in an islet. The enhanced average activity of beta cells was determined indirectly utili...
Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene ele... more Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene elektrone u atomskim orbitalama. Kisikovi radikali su najbitnija vrsta slobodnih radikala koja nastaje unutar živih bića. ROS i RNS poznati su po svojoj dvostrukoj ulozi u stanici. Jedna od uloga slobodnih radikala je da uzrokuju oksidativni stres. Organizmi su razvili različit mehanizme obrane od oksidativnog stresa. Jedan od mehanizama je i obrana enzimima oksidativnog stresa. Slobodni radikali sudjeluju i u mnogim normalnim fiziološkim procesima kao što su: redoks regulirana produkcija NO, ROS proizvodnja pomoću fagocitozne NAD(P)H oksidaze, ROS produkcija pomoću NAD(P)H oksidaze u nefagocitoznim stanicama, produkcija ROS-a kao posljedica promjene koncentracije kisika, redoks regulacija stanične adhezije, redoks regulacija imunološkog odgovora i apoptoza inducirana ROS-om. Oksidativni stres je pronađen i u različitim fiziološkim stanjima bolesti kao što su: kardiovaskularne bolesti, tumo...
U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog područja. Mjerenjem morfoloških značajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim značajkama ukazano je na morfološke razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je ključ za razlikovanje i određivanje ovih morfološki vrlo sličnih vrsta, čime bi se nadopunili opisi u postojećim europskim ključevima za trčkeThere are four species of the subgenus Eucarabus in Croatia: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi and Carabus (Eucara...
U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje četiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog područja. Mjerenjem morfoloških značajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim značajkama ukazano je na morfološke razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je ključ za razlikovanje i određivanje ovih morfološki vrlo sličnih vrsta, čime bi se nadopunili opisi u postojećim europskim ključevima za trčkeThere are four species of the subgenus Eucarabus in Croatia: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi and Carabus (Eucara...
U Hrvatskoj postoje cetiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucara... more U Hrvatskoj postoje cetiri vrste podroda Eucarabus: Carabus (Eucarabus) arvensis, Carabus (Eucarabus) catenulatus, Carabus (Eucarabus) parreyssi i Carabus (Eucarabus) ulrichi. Utvrđena je rasprostranjenost ovih vrsta u Hrvatskoj i prema tome su izrađene karte rasprostranjenosti. Vrste Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi su endemi alpsko-dinarskog podrucja. Mjerenjem morfoloskih znacajki tijela pokazano je kako se one mjenjaju s promjenom visine unutar vrsta Carabus (Eucarabus) catenulatus i Carabus (Eucarabus) parreyssi. Prema mjerenim znacajkama ukazano je na morfoloske razlike između ove dvije endemske vrste. Rezultatima mjerenja napravljen je kljuc za razlikovanje i određivanje ovih morfoloski vrlo slicnih vrsta, cime bi se nadopunili opisi u postojecim europskim kljucevima za trcke
DEAD-kutija RNA helikaza DDX5 ukljucena je u brojne stanicne procese kroz metabolizam RNA ili kao... more DEAD-kutija RNA helikaza DDX5 ukljucena je u brojne stanicne procese kroz metabolizam RNA ili kao koregulator raznih transkripcijskih faktora. U ovo
Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support... more Cholinergic innervation in the pancreas controls both the release of digestive enzymes to support the intestinal digestion and absorption, as well as insulin release to promote nutrient use in the cells of the body. The effects of muscarinic receptor stimulation are described in detail for endocrine beta cells and exocrine acinar cells separately. Here we describe morphological and functional criteria to separate these two cell types in situ in tissue slices and simultaneously measure their response to ACh stimulation on cytosolic Ca2+ oscillations [Ca2+]c in stimulatory glucose conditions. Our results show that both cell types respond to glucose directly in the concentration range compatible with the glucose transporters they express. The physiological ACh concentration increases the frequency of glucose stimulated [Ca2+]c oscillations in both cell types and synchronizes [Ca2+]c oscillations in acinar cells. The supraphysiological ACh concentration further increases the oscillation...
Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene ele... more Slobodni radikali mogu se definirati kao molekule ili dijelovi molekule koji sadrže nesparene elektrone u atomskim orbitalama. Kisikovi radikali su najbitnija vrsta slobodnih radikala koja nastaje unutar živih bica. ROS i RNS poznati su po svojoj dvostrukoj ulozi u stanici. Jedna od uloga slobodnih radikala je da uzrokuju oksidativni stres. Organizmi su razvili razlicit mehanizme obrane od oksidativnog stresa. Jedan od mehanizama je i obrana enzimima oksidativnog stresa. Slobodni radikali sudjeluju i u mnogim normalnim fizioloskim procesima kao sto su: redoks regulirana produkcija NO, ROS proizvodnja pomocu fagocitozne NAD(P)H oksidaze, ROS produkcija pomocu NAD(P)H oksidaze u nefagocitoznim stanicama, produkcija ROS-a kao posljedica promjene koncentracije kisika, redoks regulacija stanicne adhezije, redoks regulacija imunoloskog odgovora i apoptoza inducirana ROS-om. Oksidativni stres je pronađen i u razlicitim fizioloskim stanjima bolesti kao sto su: kardiovaskularne bolesti, tumo...
ObjectiveInsulin release from pancreatic beta cells is driven by cytosolic [Ca2+]c oscillations o... more ObjectiveInsulin release from pancreatic beta cells is driven by cytosolic [Ca2+]c oscillations of several different time scales that are primarily attributed to plasma membrane ion channel activity. However, the majority of past studies have been performed at supraphysiological glucose concentrations above 10 mM using electrophysiologic approaches that solely measure plasma membrane ion fluxes. The role of endoplasmic reticulum (ER) Ca2+ stores in glucose-stimulated Ca2+ signaling remains poorly understood.MethodsIn this study, we hypothesized new, brighter [Ca2+]c sensors coupled with high-resolution functional Ca2+ imaging could be used to test a previously unappreciated role for the ryanodine and IP3 intracellular Ca2+ release channels in [Ca2+]c oscillations stimulated by increases from 6 mM to 8 mM glucose.ResultsUsing mouse pancreas tissue slices exposed to physiological glucose increments, our results show that glucose-dependent activation of IP3 and ryanodine receptors prod...
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