Efficacy of Combined Insulin and Somatostatin Infusion for the Treatment of Experimental Diabetic Ketoacidosis[*]

Abstract

In order to test the efficacy of using somatostatin in the treatment of diabetic ketoacidosis, (1) saline, (2) somatostatin, (3) insulin, (4) insulin and somatostatin were infused over 2 hours in the ketoacidotic diabetic rats on the 2nd day after i.v. streptozotocin, 12 mg/100 g B.W., and plasma levels of glucagon, FFA and blood glucose and 3-hydroxybutyrate (3-OHBA) were determined.

(1) During saline infusion, significant rise of glucagon, FFA and 3-OHBA was noted. (2) Somatostatin infusion prevented the rise of glucagon and FFA, but failed to lower blood glucose, FFA and 3-OHBA. (3) Insulin infusion also prevented the rise of glucagon, and lowered glucose and 3-OHBA, but did not lower FFA. (4) Combined insulin and somatostatin infusion markedly reduced plasma glucagon level by 77 to 114 pg/ml after 30 min throughout 2 hours and decreased all the above 3 substrates levels in blood. Decrease of 3-OHBA, but not glucose was significantly greater at 30 and 60 min when compared with insulin infusion.

Suppression of glucagon secretion, and hence attenuated lipolysis and hepatic ketogenesis seemed to play a major role for the efficacy of combined infusion therapy.

The results indicate that insulin alone was not always effective for the treatment of severe diabetic ketoacidosis as evidenced by blunted antilipolytic effect. Somatostatin alone was not effective in lowering blood glucose and 3-OHBA. An addition of somatostatin to insulin infusion was most effective in the rapid reduction of 3-OHBA, suggesting efficacy of combined use of insulin and somatostatin in the treatment of diabetic ketoacidosis.

Key words

Somatostatin - Diabetic Ketoacidosis - Glucagon - Insulin - Ketone Bodies - FFA - Ketogenesise

1 This work was supported in part by a grant from the Ministry of Education (No. 257194) and Yamanouchi Grant for the study of pathophysiology of the diseases.

1 This work was supported in part by a grant from the Ministry of Education (No. 257194) and Yamanouchi Grant for the study of pathophysiology of the diseases.