Glucagon and vasopressin V1a receptor signaling in hepatocytes from aging rats

Glucose tolerance is reduced with age. The relationship between this change in glucose homeostasis and signaling of glucagon and vasopressin V1a recep tors was investigated in hepatocytes isolated from 10- and 30-month-old fem ale WAG/Rij rats. Binding capacity of hepatocytes for I-125 glucagon and H- 3 vasopressin increased 2- and 1.8-fold, respectively, between 10 and 30 mo nths. Intracellular cAMP accumulation induced by glucagon was 40% greater i n,hepatocytes of aging rats than of adults, although EC,, were similar in t he two groups. Conversely, phosphodiesterases activity and nucleotides leak age out of the cells were unchanged with age. The rise in intracellular cal cium consecutive to the stimulation of Via receptor was comparable in adult and senescent animals. Finally, glucose release by hepatocyte suspensions was greater in senescent than in adult animals in absence as in presence of glucagon. These experiments suggest that increase in glucagon receptor exp ression and cAMP generation would contribute to the impaired glucose tolera nce characteristic of the aging process. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.