Effect of glicentin-related peptides on glucagon secretion in anaesthetized dogs

Abstract

Recent studies have demonstrated that glicentin is released during nutrient ingestion. However, the biological function of glicentin remains unclear. In order to clarify the role of glicentin in the enteroinsular axis, the effect of glicentin-related peptides was investigated using in vivo local circulation of canine pancreas. Peaks I and II of gut glucagon-like immunoreactivity, partially purified from porcine intestinal extract by affinity chromatography and gel filtration, synthesized hexadecapeptide of N-terminal glicentin (1-16) and synthesized octapeptide of C-terminal glicentin (62-69) were administered for 10 min into the pancreaticoduodenal artery of canine pancreas. Blood samples were then drawn from the pancreaticoduodenal vein. The administration of peak I of glucagon-like immunoreactivity during arginine infusion in a dosage of 20 ng reduced the glucagon secretion by 42 pmol/l (p less than 0.05), whereas peak II of glucagon-like immunoreactivity (20 ng) slightly increased the plasma level of insulin, although not significantly. The administration of glicentin (1-16) in a dosage of 400 ng during saline infusion did not alter the plasma insulin level, but reduced the plasma glucagon level in the pancreaticoduodenal vein by 29 pmol/l (p less than 0.05). In addition, glicentin [62-69] in a dosage of 400 ng exerted a decrease in both the plasma insulin (40 mU/l, p less than 0.05) and glucagon level (27 pmol/l, p less than 0.05). The present study demonstrates the suppression of pancreatic glucagon release during the infusion of peak I glucagon-like immunoreactivity and N- or C-terminal glicentin-related peptide. Therefore, it is suggested that glicentin released during nutrient intake might inhibit the secretion of glucagon.

Effect of glicentin-related peptides upon the secretion of insulin and glucagon in the canine pancreas.

“…Furthermore, the C-terminal portion of glicentin (glicentin 62-69) induced an increase in insulin secretion and a decrease in glucagon secretion. The present study thus confirmed partly the results obtained in the previous study (Ohneda et al 1986). In addition, glucagon administered at the end of each experiment induced an increase in plasma insulin and at the same time a reasonable rise of plasma glucagon concentration in the pancreaticoduodenal vein.…”

“…According to the previous study (Ohneda et al 1986), both glicentin 1-16 and glicentin 62-69 induced a slight inhibition of glucagon secretion in the basal state. In the present study, in oiler to elucidate the effect of glicentin-related peptides upon the endocrine function of the pancreas much more definitely, four peptides were infused into the pancreaticoduodenal artery during arginine infusion.…”

“…In the previous study (Ohneda et al 1986), it was demonstrated that glucagon secretion from the canine pancreas was suppressed by the administration of peak I of porcine GLI, which contains glicentin, indicating that glicentin might affect the endocrine function of the pancreas. Since synthesized glicentin was not available at that time, glicentin-related peptides (glicentin 1-16 and 62-69) were investigated.…”

“…Glicentin-related pancreatic peptide (GRPP) was donated by Dr. Moody (Novo Institute, Denmark). A hexadecapeptide of the N-terminal portion of glicentin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and an octapeptide of the C-terminal portion of glicentiLn (62-69) were donated by Dr. M. Fujino (Takeda Chemical Industries, Osaka). Porcine crystalline glucagon (Lot No.…”

“…Therefore, the incretin effect of glicentin is the most interesting among its biological actions. Recently the experimental study in our laboratory suggested that administration of crude extract of peak I of gut GLI, N-terminal peptide of glicetnin (1-16) or C-terminal peptide of glicentin (62-69) suppresses the release of glucagon from the pancreas in a basal state (Ohneda et al 1986). In order to clarify the physiological role of glicentin, the present study was performed in dogs, using peptides related to glicentin.…”