RESUMO
Acid (aspartyl), basic (arginyl) and neutral (alanyl) aminopeptidases degrade angiotensins, vasopressin, oxytocin, bradykinin and enkephalins. These peptides regulate memory, energy homeostasis, water-salt balance and blood pressure, functions that are mainly exerted in the hippocampus and hypothalamus, and that can be affected by diabetes mellitus. To evaluate the relationship between the diabetes mellitus and processing and inactivation roles of these representative aminopeptidases, we measured their activities in both brain structures of control and streptozotocin-diabetic rats. Hypothalamic soluble aspartyl and arginyl aminopeptidases presented significant decreased activity levels in diabetic rats, which were mitigated by insulin therapy. In addition to membrane-bound puromycin sensitive and insensitive alanyl aminopeptidases, its soluble puromycin sensitive form did not differ between diabetic and control rats in both brain structures. Glucose and/or insulin did not seem to alter in vitro the hypothalamic activities of soluble aspartyl and arginyl aminopeptidases. The implied hypothalamic control of regulatory peptide activity by aspartyl and arginyl aminopeptidases supports the hypothesis that the hydrolytic ability of these enzyme types could be a common link for the disruptions of water-salt balance, blood pressure and energy homeostasis in diabetes mellitus.
Assuntos
Aminopeptidases/metabolismo , Encefalopatias Metabólicas/enzimologia , Encefalopatias Metabólicas/etiologia , Diabetes Mellitus Experimental/complicações , Hipocampo/enzimologia , Hipotálamo/enzimologia , Aminopeptidases/análise , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Encefalopatias Metabólicas/fisiopatologia , Antígenos CD13/análise , Antígenos CD13/metabolismo , Membrana Celular/efeitos dos fármacos , Membrana Celular/enzimologia , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Doenças do Sistema Endócrino/enzimologia , Doenças do Sistema Endócrino/etiologia , Doenças do Sistema Endócrino/fisiopatologia , Glutamil Aminopeptidase/análise , Glutamil Aminopeptidase/metabolismo , Hipocampo/fisiopatologia , Homeostase/fisiologia , Hipotálamo/fisiopatologia , Insulina/metabolismo , Insulina/farmacologia , Masculino , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neuropeptídeos/metabolismo , Inibidores da Síntese de Proteínas/farmacologia , Puromicina/farmacologia , Ratos , Ratos Wistar , Equilíbrio Hidroeletrolítico/fisiologiaRESUMO
Prolyl, cystyl and pyroglutamyl peptidases are emerging targets for diabetes and cognitive deficit therapies. The present study is focused on the influence of diabetes mellitus induced by streptozotocin on levels of representative hydrolytic activities of these enzymes in the rat hypothalamus and hippocampus. Streptozotocin-diabetic rats presented about 348mg glucose/dL blood, and a slightly increased hematocrit and plasma osmolality. The activities of soluble and membrane-bound dipeptidyl-peptidase IV, and soluble cystyl aminopeptidase did not differ between diabetic and control rats in both brain areas. Hippocampal soluble prolyl oligopeptidase presented similar activities between diabetic and controls. Increased activities in diabetics were observed for soluble prolyl oligopeptidase (1.78-fold) and membrane-bound cystyl aminopeptidase (2.55-fold) in the hypothalamus, and for membrane-bound cystyl aminopeptidase (5.14-fold) in the hippocampus. In both brain areas, the activities of membrane-bound and soluble pyroglutamyl aminopeptidase were slightly lower (<0.7-fold) in diabetics. All modifications (except hematocrit) observed in streptozotocin-treated rats were mitigated by the administration of insulin. Glucose and/or insulin were shown to alter in vitro the hypothalamic activities of soluble pyroglutamyl aminopeptidase and prolyl oligopeptidase, as well as membrane-bound cystyl aminopeptidase. These data provide the first evidence that diabetes mellitus generates direct and indirect effects on the activity levels of brain peptidases. The implied regional control of regulatory peptide activity by these peptidases suggests novel potential approaches to understand certain disruptions on mediator and modulatory functions in diabetes mellitus.
Assuntos
Diabetes Mellitus Experimental/enzimologia , Hipocampo/metabolismo , Hipotálamo/metabolismo , Peptídeo Hidrolases/metabolismo , Aminopeptidases/metabolismo , Animais , Cistinil Aminopeptidase/metabolismo , Diabetes Mellitus Experimental/tratamento farmacológico , Dipeptidil Peptidase 4/metabolismo , Glucose/farmacologia , Hipocampo/efeitos dos fármacos , Hipotálamo/efeitos dos fármacos , Técnicas In Vitro , Insulina/farmacologia , Masculino , Prolil Oligopeptidases , Ratos , Ratos Wistar , Serina Endopeptidases/metabolismo , SolubilidadeRESUMO
Acid (aspartyl), basic (arginyl) and neutral (alanyl) aminopeptidases degrade angiotensins, vasopressin, oxytocin, bradykinin and enkephalins. These peptides regulate memory, energy homeostasis, watersalt balance and blood pressure, functions that are mainly exerted in the hippocampus and hypothalamus, and that can be affected by diabetes mellitus. To evaluate the relationship between the diabetes mellitus and processing and inactivation roles of these representative aminopeptidases, we measured their activities in both brain structures of control and streptozotocin-diabetic rats. Hypothalamic soluble aspartyl and arginyl aminopeptidases presented significant decreased activity levels in diabetic rats, which were mitigated by insulin therapy. In addition to membrane-bound puromycin sensitive and insensitive alanyl aminopeptidases, its soluble puromycin sensitive form did not differ between diabetic and control rats in both brain structures. Glucose and/or insulin did not seem to alter in vitro the hypothalamic activities of soluble aspartyl and arginyl aminopeptidases. The implied hypothalamic control of regulatory peptide activity by aspartyl and arginyl aminopeptidases supports the hypothesis that the hydrolytic ability of these enzyme types could be a common link for the disruptions of watersalt balance, blood pressure and energy homeostasis in diabetes mellitus.