title: Impaired production of nerve growth factor in the submandibular gland of diabetic mice.
abstract: The production of nerve growth factor (NGF) in submandibular glands was examined in two kinds of diabetic mice. In genetically diabetic (C57BL/KsJ db/db) mice, which manifest marked insulin resistance and hyperglycemia, the concentration of NGF in the submandibular gland was less than one-tenth that of the nondiabetic controls. In streptozotocin-induced diabetic C57BL/KsJ mice, which show pancreatic insulitis leading to insulin deficiency and hyperglycemia, the glandular NGF concentration fell in a time-dependent manner to 26% of control level at 5 wk after the streptozotocin injection. A daily administration of insulin to the streptozotocin-induced diabetic mice restored the NGF concentration to almost the control level. The molecular size of NGF (13 kDa) in the glandular extracts of the genetically diabetic (db/db) mice in Western blots was indistinguishable from that of the control mice, but its level was reduced in the glands of the diabetic (db/db) animals. Although plasma NGF concentrations were normally below the sensitivity of the assay (less than 0.80 ng/ml) in both the control and the diabetic (db/db) mice, administration of cyclocytidine, which stimulates NGF release from the submandibular gland into the blood circulation, increased the plasma NGF level to 5.95 ng/ml in the control mice, but it failed to do so in the diabetic (db/db) mice. These findings suggest that, in diabetic mice, NGF production in the submandibular gland and its capacity to release NGF into the circulation are decreased.
authors.affiliation: Laboratory of Molecular and Cellular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
authors.forename: S
authors.initials: S
authors.lastname: Kasayama
authors.forename: T
authors.initials: T
authors.lastname: Oka
mesh_terms: D000818:Animals; D002470:Cell Survival; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D006943:Hyperglycemia / Q000378:metabolism; D007328:Insulin / Q000172:deficiency / Q000494:pharmacology; D007515:Islets of Langerhans / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009414:Nerve Growth Factors / Q000378:metabolism*; D013311:Streptozocin; D013363:Submandibular Gland / Q000378:metabolism*
chemical_list: D007328:Insulin; D009414:Nerve Growth Factors; D013311:Streptozocin