title: Augmented lipopolysaccharide-induction of the histamine-forming enzyme in streptozotocin-induced diabetic mice.
abstract: Disorders of the microcirculation and reduced resistance to infection are major complications in diabetes. Histamine enhances capillary permeability, and may also reduce cellular immunity. Here we demonstrate that streptozotocin (STZ)-induced diabetes in mice not only enhances the activity of the histamine-forming enzyme, histidine decarboxylase (HDC), but also augments the lipopolysaccharide (LPS)-induced elevation of HDC activity in various tissues, resulting in a production of histamine. The augmentation of HDC activity occurred as early as 2 days after STZ injection, but was not seen in nondiabetic mice. When given to STZ-treated mice, nicotinamide, an inhibitor of poly(ADP-ribose) synthetase, reduced both the elevation of blood glucose and the elevations of HDC activity and histamine production. These results suggest that hyperglycemia may initiate a sequence of events leading not only to an enhancement of basal HDC activity, but also to a sensitization of mice to the HDC-inducing action of LPS. We hypothesize that bacterial infections and diabetic complications may mutually exacerbate one another because both involved an induction of HDC.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Graduate School of Dentistry, Tohoku University, 4-1 Seiryo-machi, Aoba-ku, 980-8575, Sendai, Japan.
authors.forename: Senri
authors.initials: S
authors.lastname: Oguri
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Motegi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Endo
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D006632:Histamine / Q000032:analysis / Q000096:biosynthesis; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009536:Niacinamide / Q000494:pharmacology; D013311:Streptozocin / Q000037:antagonists & inhibitors; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D001786:Blood Glucose; D008070:Lipopolysaccharides; D009536:Niacinamide; D013311:Streptozocin; D006632:Histamine; D006640:Histidine Decarboxylase