ABSTRACT-We investigated the effects of the salivary peptide P-C (P-C), a saliva-derived peptide, on glucose (8.3 mM)-and arginine (10 mM)-induced insulin release and arginine (10 mM)-induced glucagon release using the perfused pancreas of spontaneously diabetic GK rats. Both its potentiating effect on insulin release and its inhibitory effect on glucagon release were concentration-dependent in diabetic GK rats. The ratio of insulin release obtained with P-C (194 nM) to that without P-C in GK rats was the same as ratio in normal Wistar rats. The ratio (0.40) of glucagon release obtained with P-C (194 nM) to that without P-C was smaller in diabetic GK rats than that (0.75) in normal Wistar rats. These results indicate that P-C inhibits arginine-induced glucagon release in diabetic GK rat pancreas more effectively than in normal Wistar rat pancreas.Keywords: Salivary peptide P-C, Insulin release, Inhibition of glucagon release, Pancreas (perfused), Diabetic GK rat Salivary peptide P-C (P-C) isolated from human saliva is a proline-rich polypeptide comprising 44 amino acid residues (1, 2). From immunohistochemical studies, P-Clike immunoreactivity is found in human pancreatic B cells (3), being localized in the insulin secretory granules of these cells (4). A decrease in positive immunofluorescence due to P-C-like immunoreactivity has been reported in the pancreas of diabetic (non-insulin-dependent diabetes mellitus, NIDDM) patients (5, 6). Therefore, a decrease in the level of P-C may accompany the occurrence of diabetes.In a previous study, we reported that P-C has an antihyperglycemic effect on alloxan-induced diabetic mice (7) and that P-C remarkably potentiates glucose (8.3 and 16.7 mM)-induced insulin release and inhibits arginine (10 mM)-induced glucagon release in a concentration-dependent manner in the isolated perfused pancreas of normal Wistar rats (8).The aim of the present study was to determine whether P-C modulates insulin and glucagon release using the isolated perfused pancreas of GK rats, a spontaneous NIDDM (Type II) model not exhibiting obesity (9-11).
MATERIALS AND METHODSMale GK (Goto-Kakizaki) rats (18-to 20-weeks-old; body weight, 348 -393 g; blood glucose levels, 208 -260 mg/dl) were used as the diabetic rats, and they were compared with age-matched normal male Wistar rats (body weight, 474-512 g; blood glucose levels, 92-122 mg/dl), which served as the controls. GK rats (SPF) were donated by Dr. Kenichi Suzuki (Faculty of Medicine, Tohoku University, Sendai) and inbred in our laboratory. Normal Wistar rats were purchased from Sankyo Labo Service (Tokyo). Perfusion of the isolated pancreas was carried out as described previously (8). The perfusate was a basal medium of Krebs-Ringer bicarbonate buffer solution (pH 7.4) containing 0.5010 bovine serum albumin (Fraction V; Sigma, St. Louis, MO, USA), 2% dextran (T-70; Pharmacia, Uppsala, Sweden) and 2.8 MM D-glucose (12) saturated with a gas mixture of 95010 02 and 5% CO2. The test substances were dissolved in the basal medium at room temperatur...