Altered beta-endorphin, Met- and Leu-enkephalins, and enkephalin-containing peptides in pancreas and pituitary of genetically obese diabetic (db/db) mice during development of diabetic syndrome.
We have recently shown that in addition to beta-endorphin the opioid peptides Met- and Leu-enkephalin and their apparent precursors are localized in islet endocrine cells of the rat pancreas. To begin evaluating a possible role for these pancreatic opiates in the pathophysiology of genetic diabetes in rodents, immunoreactive beta-endorphin and Met- and Leu-enkephalins were measured in acetic acid extracts of pancreas and pituitary of C57BL/KsJ db/db mice and their lean littermates. Groups of animals were studied during three phases of development of the diabetic syndrome in the mutant mice: at 4 (hyperinsulinemic and prediabetic); 6, 9, and 12 (frankly obese and diabetic); and 30 (hypoinsulinemic) wk of age. Elevations or decreases (P less than .05) were found in db/db mice (vs. lean littermates) as follows: pituitary content of Met-enkephalin was twofold higher at all ages studied; pituitary free Leu-enkephalin was lower at 4 wk and reversed to higher at 6-30 wk; pancreatic beta-endorphin was 30% lower at 4 wk and reversed to threefold higher at 6-12 wk; Met- and Leu-enkephalin-containing larger peptides were elevated at one or more points between 6 and 12 wk in both the pancreas and the pituitary. Thus, the onset of overt obesity between 4 and 6 wk of age was accompanied by a marked rise in both pancreatic beta-endorphin and pituitary Leu-enkephalin; similar elevations in these parameters have been reported previously in C57BL/6J ob/ob mice at approximately 12 wk of age.(ABSTRACT TRUNCATED AT 250 WORDS)
D000375:Aging; D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism*; D004743:Enkephalin, Leucine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007515:Islets of Langerhans / Q000378:metabolism*; D051379:Mice; D008820:Mice, Obese / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism*; D001615:beta-Endorphin
D004723:Endorphins; D004745:Enkephalins; D007328:Insulin; D004744:Enkephalin, Methionine; D004743:Enkephalin, Leucine; D001615:beta-Endorphin