Immunoreactive neurotensin in spontaneous syndromes of obesity and diabetes in mice.

Immunoreactive neurotensin was measured in plasma and acid-ethanol extracts of brain, intestine and pancreas of obese hyperglycaemic (ob/ob) mice of the Aston strain, C57BL/KsJ diabetes-obese (db/db) mice, and their respective lean controls. In lean mice, the intestine was the major source of neurotensin (156-194 mg/g wet weight and 169-361 ng/intestine), with smaller amounts in the brain (33-43 ng/g and 13-17 ng/brain), pancreas (0.8-1.1 ng/g and 0.28-0.32 ng/pancreas) and plasma (50-100 pg/ml). Compared with lean controls, ob/ob and db/db mice exhibited 13 and 23% decreases in brain weight, and 37 and 82% increases in intestinal weight. Concentrations of neurotensin in plasma and brain were similar in lean and obese-diabetic mutant mice, but the total content of brain neurotensin was 25% lower in ob/ob mice. Neurotensin was unchanged in the pancreas of db/db mice. However, raised concentrations and total contents of neurotensin were observed in the pancreas of ob/ob mice (72 and 57%, respectively) and the intestine of both ob/ob (56 and 118%) and db/db (35 and 144%) mice. These observations raise the possibility that increased neurotensin concentrations might exert local effects in the intestine and pancreas which contribute to the pathogenesis of obesity-diabetes syndromes in mice.