Impaired hepatic metabolism of somatostatin-14 and somatostatin-28 in spontaneously diabetic BB rats.
Somatostatin-14 (S-14) and somatostatin-28 (S-28) circulate in normal portal plasma and are rapidly metabolized by the liver. In the present study we have investigated the hepatic clearance of the two peptides in insulinopenic diabetes using as a model spontaneously diabetic BB rats. Isolated livers from three groups of five nondiabetic, untreated diabetic, or insulin-treated diabetic animals were perfused with synthetic S-14 or S-28. The metabolism of the two peptides was monitored as S-14-like immunoreactivity by RIA using antibody R149 specific for the central segment of S-14, which detects S-14 and S-28 equally. The t1/2 and hepatic extraction of S-14 in untreated diabetic rats (25.9 +/- 2.6 min and 27.1 +/- 4.6%, respectively) were significantly different (P less than 0.01) compared with nondiabetic control values (13.3 +/- 1.1 min and 42.8 +/- 2.5%) and were normalized with insulin treatment (13.1 +/- 1.0 min and 42.0 +/- 2.3%). Similarly, the t1/2 of S-28 disappearance and the hepatic extraction of the peptide in untreated diabetic rats (62.1 +/- 1.8 min and 9.8 +/- 0.6%) were also significantly different (P less than 0.05) from nondiabetic control values (44.0 +/- 1.9 min and 13.7 +/- 1.6%) and were normalized with insulin treatment (47.2 +/- 2.0 min and 13.1 +/- 1.8%). Sephadex G-50 gel chromatography of media after S-28 perfusion showed two peaks of S-14-like immunoreactivity corresponding to S-28 and S-14. The extent of S-28 to S-14 conversion varied from 10% in 10-min perfusion samples to 30% in 60-min samples and was identical in normal and untreated diabetic rats. We conclude that 1) S-14 is metabolized more rapidly than S-28 by livers of both normal and diabetic rats; 2) the hepatic extraction of S-14 and S-28 is significantly impaired in insulin-deficient diabetic rats and normalized with insulin treatment; and 3) S-28 is significantly converted to S-14 equally in normal and diabetic rats.
D000818:Animals; D002850:Chromatography, Gel; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006207:Half-Life; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D051381:Rats; D013004:Somatostatin / Q000378:metabolism*; D053561:Somatostatin-28
D013004:Somatostatin; D053561:Somatostatin-28