Sıçanlarda glukoz homeostazının düzenlenmesinde glukagonun merkezi sinir sistemindeki etkilerinin araştırılması
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Tarih
2020
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İnönü Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Amaç: Kan glukoz homeostazının sağlanmasında glukoz metabolizmasının kontrolünde önemli olan hormonal mekanizmaların düzenlenmesi esastır. Bu çalışmanın amacı merkezi glukagonun akut ve uzun süreli infüzyonunun MSS'deki muhtemel etkisinin pankreasın endokrin salgıları üzerindeki düzenleyici rolünü aydınlatmaktır. Materyal ve Metot: Çalışma akut (120 dk) ve uzun (7 gün) intraserebrovasküler (icv) glukagon uygulanan iki ayrı protokol şeklinde planlandı. Glukagon ve çözücü (yapay Beyin Omurilik Sıvısı; yBOS) pankreatik denervasyondan (PD) sonra akut gruplarda mikro enjektör, uzun süreli gruplarda ozmotik mini pompa (1µg/10µl/dk) ile icv uygulandı. 90 adet 220-280 g ağırlığında erkek Wistar albino sıçan Kontrol, yBOS (120 dk), Glukagon (120 dk), PD+yBOS (120 dk), PD+Glukagon (120 dk), yBOS (7 gün), Glukagon (7 gün), PD+yBOS (7 gün), PD+Glukagon (7gün) olacak şekilde gruplara (n=10) ayrıldı. ELISA yöntemi ile serum glukagon, insülin ve epinefrin seviyeleri, beyin AgRP/POMC ve pakreas insülin/glukagon seviyeleri Western Blot ve immünofloresan yöntemiyle değerlendirildi. Bulgular: Kısa süreli icv glukagon uygulamasının etkilerinin incelendiği protokolde glukagon seviyesindeki artış ve kan glukozu, insülin ve glukagon seviyelerindeki azalma kontrol grubuna göre istatistiksel olarak anlamlıdır (p≤0.05). Glukagon uygulamasının uzun süreli etkilerinin incelendiği protokolde yBOS (7 gün) grubuyla kıyaslandığında, PD (7 gün) ve PD+Glukagon (7 gün) gruplarında POMC ve AgRP seviyelerinde azalma istatistiksel olarak anlamlıdır (p≤0.05). PD (7 gün), Glukagon (7 gün) ve PD+Glukagon (7 gün) uygulanan gruplarda yem tüketimi ve vücut ağırlığındaki artış, pankreas glukagon seviyelerindeki artış ve insülin seviyelerindeki azalma kontrol grubu ile kıyaslandığında istatistiksel olarak anlamlıdır (p≤0.05). Sonuç: Çalışma bulgularımız glukagonun glukoz homeostazı üzerinde kan glukozu ve otokrin etkilerin yanısıra çok daha fazla rolü olabileceğini ve bu etkinliğini hem periferal hem de merkezi olarak iştahın düzenlenmesinde de rolünün olabileceğine dair kanıtlar sağlamıştır. Pankreastan salgılanan glukagon beyinde bir nörohormon gibi etki göstererek kan glukozunda etkili olan merkezi yolaklarında uyarımını sağlamıştır. Anahtar Kelimeler: Beyin, Glukagon, Glukoz homeostazı, İnsülin, Pankreas
Aim: The regulation of hormonal mechanisms that are important in the control of glucose metabolism is essential in maintaining blood glucose homeostasis. This study aims to elucidate the posibble effect of the acut/long term infusion of central glucagon on the CNS as the regulatory role on the endocrine secretions of the pancreas. Materials and Methods: This study was planned as two separate protocols to examine acute (120 min) and long term (7 days) intracerebrovascular (icv) glucagon effect. Glucagon and solvent (artificial Cerebrospinal Fluid; aCSF) were administered after pancreatic denervation (PD) by micro injector and osmotic mini pump (1µg/10µl/min) in acute and long-term groups respectively. 90 male Wistar albino rats weighing 220-280 g Control, aCSF (120 min), Glucagon (120 min), PD+ aCSF (120 min), PD+Glucagon (120 min), aCSF (7 days), Glucagon (7 days), PD+aCSF (7 days), PD+Glucagon (7 days) were divided into groups (n = 10). Serum glucagon, insulin and epinephrine levels analyzed by ELISA method, brain AgRP/POMC and pacreatic insulin/glucagon levels were evaluated by western and IF method. Results: In the protocol in which the effects of short-term icv glucagon administration were examined, the increase in glucagon level and the decrease in blood glucose, insulin and glucagon levels were statistically significant compared to the control group (p≤0.05). In the protocol where the long-term effects of glucagon administration were examined, the decrease in POMC and AgRP levels in PD (7 days) and PD+Glucagon (7 days) groups was statistically significant when compared to the aCSF (7 days) group (p≤0.05). Increase in feed consumption and body weight, pancreatic glucagon levels and decrease in insulin levels in PD (7 days), Glucagon (7 days) and PD+Glucagon (7 days) groups were statistically significant compared to the control group (p≤0.05). Conclusions: Our study findings provided evidence that glucagon may have a much greater role in glucose homeostasis besides blood glucose and autocrine effects, and that this activity may have a role in appetite regulation both peripherally and centrally. In addition, glucagon secreted from the pancreas acted as a neurohormone in the brain, stimulating the central pathways on blood glucose. Key words: Brain, Glucagon, Glucose homeostasis, Insulin, Pancreas
Aim: The regulation of hormonal mechanisms that are important in the control of glucose metabolism is essential in maintaining blood glucose homeostasis. This study aims to elucidate the posibble effect of the acut/long term infusion of central glucagon on the CNS as the regulatory role on the endocrine secretions of the pancreas. Materials and Methods: This study was planned as two separate protocols to examine acute (120 min) and long term (7 days) intracerebrovascular (icv) glucagon effect. Glucagon and solvent (artificial Cerebrospinal Fluid; aCSF) were administered after pancreatic denervation (PD) by micro injector and osmotic mini pump (1µg/10µl/min) in acute and long-term groups respectively. 90 male Wistar albino rats weighing 220-280 g Control, aCSF (120 min), Glucagon (120 min), PD+ aCSF (120 min), PD+Glucagon (120 min), aCSF (7 days), Glucagon (7 days), PD+aCSF (7 days), PD+Glucagon (7 days) were divided into groups (n = 10). Serum glucagon, insulin and epinephrine levels analyzed by ELISA method, brain AgRP/POMC and pacreatic insulin/glucagon levels were evaluated by western and IF method. Results: In the protocol in which the effects of short-term icv glucagon administration were examined, the increase in glucagon level and the decrease in blood glucose, insulin and glucagon levels were statistically significant compared to the control group (p≤0.05). In the protocol where the long-term effects of glucagon administration were examined, the decrease in POMC and AgRP levels in PD (7 days) and PD+Glucagon (7 days) groups was statistically significant when compared to the aCSF (7 days) group (p≤0.05). Increase in feed consumption and body weight, pancreatic glucagon levels and decrease in insulin levels in PD (7 days), Glucagon (7 days) and PD+Glucagon (7 days) groups were statistically significant compared to the control group (p≤0.05). Conclusions: Our study findings provided evidence that glucagon may have a much greater role in glucose homeostasis besides blood glucose and autocrine effects, and that this activity may have a role in appetite regulation both peripherally and centrally. In addition, glucagon secreted from the pancreas acted as a neurohormone in the brain, stimulating the central pathways on blood glucose. Key words: Brain, Glucagon, Glucose homeostasis, Insulin, Pancreas
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Tanbek, K. Sıçanlarda glukoz homeostazının düzenlenmesinde glukagonun merkezi sinir sistemindeki etkilerinin araştırılması, Yayınlanmış Doktora Tezi, 2021, İnönü Üniversitesi.
