Hypothalamic glucagon signaling in fasting hypoglycemia
2016
Pitchaimani, Vigneshwaran | Arumugam, Somasundaram | Thandavarayan, Rajarajan Amirthalingam | Karuppagounder, Vengadeshprabhu | Afrin, Mst Rejina | Sreedhar, Remya | Harima, Meilei | Suzuki, Hiroshi | Miyashita, Shizuka | Suzuki, K. (Kenji) | Nakamura, Masahiko | Ueno, Kazuyuki | Watanabe, Kenichi
Sustained glucagon infusion increases hepatic glucose production, but this effect is transient due to hypothalamic glucagon signaling. In hypoglycemia, glucagon acts as a major defense to sustain the blood glucose level and this raises the question regarding glucagon signaling associated glucose production in prolonged fasting hypoglycemia. In this study, we investigated the proteins associated with hypothalamic glucagon signaling and liver gluconeogenesis during fasting hypoglycemia.8–9week old, male C57BL6/J mice were fasted for 4, 8, 12, 18, 24, 30, 36 or 42h. In the hypothalamus, we investigated glucagon signaling by analyzing the glucagon receptor and its downstream protein, peroxisome proliferator-activated receptor-gamma coactivator 1 (PGC-1) expression. In the liver, we investigated gluconeogenesis by analyzing p-protein kinase A (PKA)Sᵉʳ/ᵀʰʳ substrate and phosphoenolpyruvate carboxykinase — cytosolic (PEPCK-C) expression using the western blotting technique.The elevated or trended higher hypothalamic glucagon receptor and PGC-1 expressions at 18 and 42h were correlated with the attenuated liver p-PKASᵉʳ/ᵀʰʳ substrate expression. The attenuated hypothalamic glucagon receptor and PGC-1 expressions at 12, 24, 30 and 36h were correlated with the elevated or trended higher liver p-PKASᵉʳ/ᵀʰʳ substrate expression.The hypothalamic glucagon signaling during fasting hypoglycemia might have been modulated by circadian rhythm and this possibly attenuates the liver p-PKASᵉʳ/ᵀʰʳ substrate to modify the gluconeogenesis pathway. This mechanism will help to understand the hyperglucagonemia associated complications in diabetes.
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