Insulin hypersecretion and potentiation of endotoxin shock in the rat.
Endotoxin has been shown to disrupt the metabolic regulation of blood glucose and insulin levels. This study determined the effect of arginine on plasma glucose and insulin regulation during endotoxicosis in order to assess its contribution to glucose dyshomeostasis in the pathogenesis of endotoxin shock. In addition, the ability of arginine to stimulate insulin secretion from the endotoxic pancreas was assessed directly by using the in vitro perfused rat pancreas model. Arginine significantly increased the lethal effects of endotoxin in rats and shortened the time course to death. Rats treated with both arginine and endotoxin demonstrated 1) a rapidly ensuing hypoglycemia, 2) an absence of the characteristic endotoxin-induced hyperglycemia, and 3) a rapidly progressive and profound hypoglycemia. In contrast alanine (which does not stimulate insulin secretion) did not profoundly exacerbate the glucose dyshomeostases of endotoxin shock. Lastly, arginine induced a hypersecretion of insulin as directly determined from the in vitro perfused pancreas of the endotoxic rat. These results demonstrated that arginine, through its direct insulinotropic effect on the hypersecretory endotoxic pancreas, contributed to the endotoxic hyperinsulinemia and thereby accelerated the development of glucose dyshomeostasis and lethal hypoglycemia in the endotoxic rat. This study has emphasized the important role for insulin in the pathogenesis of endotoxin-induced hypoglycemia. Furthermore, the potential role of insulin secretagogues other than glucose has been identified with regard to the insulin hypersecretory state of the endotoxic pancreas.
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D006706:Homeostasis; D006946:Hyperinsulinism / Q000378:metabolism*; D007328:Insulin / Q000097:blood / Q000378:metabolism; D000078790:Insulin Secretion; D008297:Male; D010179:Pancreas / Q000378:metabolism / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D012772:Shock, Septic / Q000378:metabolism* / Q000401:mortality / Q000503:physiopathology
D001786:Blood Glucose; D007328:Insulin; D001120:Arginine; D000409:Alanine