Augmentation of endotoxic lethality and glucose dyshomeostasis by phorbol ester
| Autor: | H. Inaba, J. P. Filkins |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
Blood Glucose
Male Pentobarbital medicine.medical_specialty Physiology Sodium medicine.medical_treatment chemistry.chemical_element Biology chemistry.chemical_compound In vivo Physiology (medical) Internal medicine medicine Hyperinsulinemia Animals Homeostasis Insulin Lactic Acid Protein kinase C Dimethyl sulfoxide Glucose Tolerance Test medicine.disease Shock Septic Rats Endocrinology chemistry Phorbol Lactates Tetradecanoylphorbol Acetate medicine.drug |
| Zdroj: | The American journal of physiology. 260(3 Pt 2) |
| ISSN: | 0002-9513 |
| Popis: | To investigate the role of protein kinase C (PKC) activation in the pathogenesis of endotoxin (ETX) shock, the in vivo effects of phorbol 12-myristate 13-acetate (PMA) on ETX-induced lethality and glucose dyshomeostasis were determined. Fed rats (300-400 g) were treated intravenously with incremental doses of Salmonella enteritidis ETX and either the vehicle, 110 mg/kg ip dimethyl sulfoxide (DMSO), or 0.5 mg/kg ip PMA dissolved in DMSO. PMA significantly increased ETX-induced lethality to doses of 1.0-20 mg/kg. PMA augmented the initial hyperglycemia, late hypoglycemia, and hyperlactacidemia after 1 mg/kg iv ETX to rats anesthetized with pentobarbital sodium. In contrast, 4 alpha-phorbol, a phorbol derivative that does not activate PKC, had no effect on either lethality or the glucose and lactate responses. Hyperinsulinemia after 1 mg/kg iv ETX was prolonged by PMA but not by 4 alpha-phorbol. Insulin tolerance testing (0.5 U/kg iv) produced an exaggerated hypoglycemic response in PMA-treated endotoxic (0.33 mg/kg) rats. Glucose tolerance to 1.2 g/kg iv was increased by ETX and PMA attenuated the increased tolerance. Thus PKC activation may be involved in the pathogenesis of lethal endotoxicosis and associated glucose dyshomeostasis. |
| Databáze: | OpenAIRE |
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