腸管グルカゴンに及ぼす下垂体の影響

抄録

It has been reported that gut glucagon immunoreactivity (Gut GI) and gut glucagon-like immunoreactivity (Gut GLI) increase markedly day by day in total pancreatectomized dogs without insulin injections. However, the regulation mechanism of the release of Gut GI and Gut GLI has still not been completely resolved.
The present studies were designed to find a part of the regulation mechanism of the release of Gut GI and Gut GLI in connection with hypophysis and also to examine the relation between gut glucagon and blood sugar levels after pancreatectomy.
Eight healthy mongrel dogs, weighing 10-13 Kg, which had fasted for twelve hours, were used. Under Ketalar and also Ravonal anesthesia, total pancreatectomy of these dogs was performed through a midline abdominal incision. Thereafter, these dogs were maintained without insulin therapy for three days. On the fourth day, under Ketalar anesthesia, the hypophysis of these dogs was removed under the direct vision through the temporal approach. Then for one day after this operation, these dogs were kept without further insulin and other hormone injections. On the next day, hypophyses of other dogs were transplanted individually into the hypoderm of the heads of these dogs. As controls, ten other dogs were used. Then total pancreatectomy was performed. These dogs were kept under nontreatment for eight days. In all these dogs, blood was sampled through the polyethylene catheter inserted into the femoral vein in the fasting state early every morning for eight days. The blood samples were assayed for blood sugar by the glucose oxidase method, immunoreactive insulin (IRI) by the double antibody method, and immunoreactive glucagon (IRG) by the talc method : glucagon immunoreactivity (GI), by using antibody “K30” highly specific for pancreatic glucagon (Unger, Texas), and total glucagon-like immunoreactivity (total GLI) by using a nonspecific glucagon antibody “K4023” (Novo, Denmark). This difference between total GLI and GI was considered to be Gut GLI.
1) In the control experiment of only total pancreatectomy, blood sugar levels showed significant increases (P<0.001) from 107±7 mg/dl, the value before the operation, to 306±24 mg/dl on the day after the operation; thereafter, they increased gradually, rising to a maximum of 756±124 mg/dl on the eighth day. IRI differed less than 5 μU/ml (P<0.05~0.01) in all the days after pancreatectomy from 14±2 μU/ml, the value before the operation. GI rose significantly (P<0.001) from 70±6 pg/ml, the value before the operation, to 251±32 pg/ml on the second day after the operation and thereafter showed a gradual increase, rising to a maximum of 680±167 pg/ml on the eighth day. Gut GLI increased significantly from 175±7 pg/ml, the value before the operation, to 452±74 pg/ml (P<0.01) on the second day after the operation and to 648±50 pg/ml (P<0.001) on the third day; thereafter, it remained stable at about 650 pg/ml until the eighth day. (Fig. 1)
2) In the hypophysectomized dogs after total pancreatectomy, blood sugar levels decreased significantly (P<0.05) from 362±22 mg/dl, the value before hypophysectomy, to 278±24 mg/dl on the day after hypophysectomy, and to 255±21 mg/dl, still lower on the second day. GI showed a significant decrease (P<0.05) from 438±36 pg/ml, the value before hypophysectomy, to 305±46 pg/ml on the day after the operation and to 262±52 pg/ml on the second day. However, Gut GLI showed no significant changes after hypophysectomy. (Fig. 2)
3) In the dogs which received hypophysis-transplantation after hypophysectomy following total pancreatectomy, blood sugar levels increased significantly (P<0.05) from 255±21 mg/dl, the value before transplantation. to 359±35 mg/dl on the second day after transplantation.