Molecular target structures in alloxan-induced diabetes in mice

Walde, Sabine Schulte im; Dohle, Claudia; Schott-Ohly, Patricia; Gleichmann, Helga

doi:10.1016/s0024-3205(02)01918-5

Cited by 58 publications

(36 citation statements)

References 39 publications

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“…2). Interestingly, glucose but not 5TG can block the cytotoxic effect of alloxan on ␤-cells [58]. Taken together, these data suggest that alloxan and 5TG might act on different glucosensing cell populations in this brain area, one dependent upon GK and the other not.…”

Section: Physiologic Functions Of Putative Gk-containing Glucosensingmentioning

confidence: 78%

Anatomy, Physiology and Regulation of Glucokinase as a Brain Glucosensor

Levin¹,

Routh²,

Sanders³

et al. 2004

Frontiers in Diabetes

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The brain has evolved specialized glucosensing neurons which participate in glucose and overall energy homeostasis in the body. Glucosensing neurons utilize glucose as a signaling molecule to alter their firing rate, as opposed to the vast majority of neurons which primarily utilize glucose to fuel their metabolic needs [1]. Oomura [2] and Anand [3] and their co-workers first demonstrated such neurons in both the fore-and hindbrain in 1964. Although these neurons can respond directly or indirectly to either the complete absence of glucose or to levels as high as 20 mM [4][5][6][7][8][9][10][11], it is likely that their primary range is between 0.5-3.5 mM under physiologic conditions [12,13]. Mounting evidence supports a role for glucokinase (GK) as the gatekeeper for neuronal glucosensing within this physiologic range [11,14]. Importantly, glucosensing neurons reside in brain areas known to play critical regulatory roles in energy homeostasis and neuroendocrine and autonomic function [15][16][17][18].Glucose sensing neurons are either excited (glucose excited; GE) or inhibited (glucose inhibited; GI) by rising ambient glucose levels [6,7,9,10]. However, early studies used extracellular recording techniques to monitor neuronal activity at glucose levels virtually never seen by the living brain, i.e. 0 vs. 10-20 mM [6,10]. Neurophysiologic studies have provided direct evidence that GE neurons function much like the pancreatic ␤-cell where elevated glucose levels increase the ATP/ADP ratio and inactivate (close) an inwardly rectifying K ϩ pore-forming unit (Kir6.2) of the ATP-sensitive K ϩ (K ATP ) channel [4,5,9,10,19]. This channel on GE neurons is similar, but not completely identical to

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Section: Physiologic Functions Of Putative Gk-containing Glucosensingmentioning

confidence: 78%

Anatomy, Physiology and Regulation of Glucokinase as a Brain Glucosensor

Levin¹,

Routh²,

Sanders³

et al. 2004

Frontiers in Diabetes

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“…Alloxan-induced diabetes is a common experimental model used to study the pathophysiologic mechanisms involved in type 1 diabetes (39). Blood glucose levels in diabetic mice were increased 10 d after alloxan administration (Supplemental Fig.…”

Section: Diabetic Mice Showed Increased MC Numbers After Msmentioning

confidence: 99%

Histamine H2 Receptor Signaling in the Pathogenesis of Sepsis: Studies in a Murine Diabetes Model

Carlos

Spiller

Souto

et al. 2013

The Journal of Immunology

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Type 1 diabetes enhances susceptibility to infection and favors the sepsis development. In addition, diabetic mice produced higher levels of histamine in several tissues and in the blood after LPS stimulation than nondiabetic mice. In this study, we aimed to explore the role of mast cells (MCs) and histamine in neutrophil migration and, consequently, infection control in diabetic mice with mild sepsis (MS) induced by cecum ligation and puncture. We used female BALB/c, MC-sufficient (WB/B6), MC-deficient (W/Wv), and NOD mice. Diabetic mice given MS displayed 100% mortality within 24 h, whereas all nondiabetic mice survived for at least 5 d. The mortality rate of diabetic mice was reduced to 57% after the depletion of MC granules with compound 48/80. Moreover, this pretreatment increased neutrophil migration to the focus of infection, which reduced systemic inflammatory response and bacteremia. The downregulation of CXCR2 and upregulation of G protein–coupled receptor kinase 2 in neutrophils was prevented by pretreatment of diabetic mice given MS with compound 48/80. In addition, blocking the histamine H2 receptor restored neutrophil migration, enhanced CXCR2 expression, decreased bacteremia, and improved sepsis survival in alloxan-induced diabetic and spontaneous NOD mice. Finally, diabetic W/Wv mice had neutrophil migration to the peritoneal cavity, increased CXCR2 expression, and reduced bacteremia compared with diabetic WB/B6 mice. These results demonstrate that histamine released by MCs reduces diabetic host resistance to septic peritonitis in mice.

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“…Kerusakan DNA tersebut menstimulasi poly ADP-ribosylation, proses yang terlibat pada DNA repair. Adanya ion ferro dan hidrogen peroksida membentuk radikal hidroksi yang sangat reaktif melalui reaksi fenton (Wilson et al, 1984;Szkudelski, 2001;Walde et al, 2002).…”

Section: Aloksanunclassified

“…Pada kondisi tersebut, konsentrasi insulin meningkat sangat cepat, dan secara signifikan mengakibatkan gangguan pada sensitivitas insulin perifer dalam waktu singkat. Selain kedua faktor tersebut di atas, aloksan juga diduga berperan dalam penghambatan glukokinase dalam proses metabolisme energi (Szkudelski, 2001;Walde et al, 2002).…”

Section: Aloksanunclassified

Review : Animal Models Of Diabetes Mellitus : Pathology And Mechanism Of Some Diabetogenics

Nugroho

2006

Biodiversitas

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Animal models of diabetes mellitus were made and used in laboratorium according to the pathology of diabetic patient and its complications. Animal models of diabetes mellitus were designed by two methods: induced method such as pancreatectomy, chemicals (diabetogenic), viruses, and spontaneous method such BB (bio breeding) rats and NOD (non-obese diabetic) mice. The techniques of animal models of diabetes mellitus frequently used in the research were usage of diabetogenic such as alloxan and streptozotocin. Alloxan and its reduction metabolite (dialuric acid) establish a redox cycle and form superoxide radicals, and they undergo dismutation to hydrogen peroxide. By Fenton reaction, the formation of reactive hydroxyl radicals was stimulated. These radicals with high concentration of cytosolic calcium cause rapid destruction of β cells. Besides, streptozotocin enters the β cell through a glucose transporter (GLUT2), and stimulates superoxide radicals, hydrogen peroxide and hydroxyl radicals which in turn causes rapid destruction of β cells. Streptozotocin also releases toxic amounts of nitric oxide that inhibits aconitase activity and contributes in DNA damage. . © 2006 Jurusan Biologi FMIPA UNS SurakartaKey words: animal models, diabetes mellitus, alloxan, streptozotocin. PENDAHULUANPercobaan mengenai diabetes mellitus dengan menggunakan hewan percobaan didasarkan pada patogenesis penyakit tersebut pada manusia. Penelitian menggunakan hewan percobaan yang dibuat secara patologis menderita diabetes mellitus, telah banyak penemuan mengenaii bermacam-macam diagnosa, terapi maupun obat-obat yang digunakan dalam penanganan penyakit diabetes mellitus. Meskipun demikian, kondisi patologis hewan percobaan tersebut tidak sepenuhnya menggambarkan kondisi patologis secara riil pada manusia. Hal ini disebabkan karena beberapa hal antara lain : perbedaan kondisi fisiologi, perbedaan patologis dari beberapa model diabetes mellitus, ragamnya penyakit diabetes mellitus, serta aadanya komplikasi yang menyertai dari penyakit tersebut. Menurut Cheta (1998), berdasarkan cara pembuatannya, hewan percobaan diabetes mellitus dibedakan menjadi dua yaitu : (1) terinduksi (induced), misalnya melalui pankreaktomi, senyawa kimia (diabetogenik) dan virus; (2) spontan (spontaneous), misalnya menggunakan tikus BB (bio breeding) atau mencit NOD (non-obese diabetic). Spontaneous animal models mempunyai karakteristik yang relatif sama dengan kondisi diabetes mellitus pada manusia meliputi gejalagejala penyakit, imunologi, genetik maupun karakteristik klinik lainnya. Pada tulisan ini akan disajikan macammacam hewan percobaan diabetes mellitus, dan selanjutnya akan ditekankan pada mekanisme molekular dua diabetogenik yang sering digunakan yaitu streptozotosin dan aloksan. DIABETES MELLITUS DefinisiDiabetes diturunkan dari bahasa Yunani yaitu diabêtês yang berarti pipa air melengkung (syphon). Diabetes dinyatakan sebagai keadaan di mana terjadi produksi urin yang melimpah pada penderita (Lawrence, 1994). Diabetes mellitus (DM) merupakan suat...

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Molecular target structures in alloxan-induced diabetes in mice

Cited by 58 publications

References 39 publications

Anatomy, Physiology and Regulation of Glucokinase as a Brain Glucosensor

Anatomy, Physiology and Regulation of Glucokinase as a Brain Glucosensor

Histamine H2 Receptor Signaling in the Pathogenesis of Sepsis: Studies in a Murine Diabetes Model

Review : Animal Models Of Diabetes Mellitus : Pathology And Mechanism Of Some Diabetogenics

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