title: Effects of Diabetes on Salivary Gland Protein Expression of Tetrahydrobiopterin and Nitric Oxide Synthesis and Function.
abstract: Xerostomia is defined as dry mouth resulting from a change in the amount or composition of saliva and is often a major oral health complication associated with diabetes mellitus (DM). Studies have shown that xerostomia is more common in females at the onset of DM. Evidence suggests that nitric oxide (NO) plays a critical role in healthy salivary gland function. However, the specific mechanisms by which NO regulates salivary gland function at the onset of DM have yet to be determined. This study has two aims: 1) to determine whether protein expression or dimerization of NO synthase enzymes (neuronal [nNOS] and endothelial [eNOS]) are altered in the onset of diabetic xerostomia; and 2) to determine whether the changes in nNOS/eNOS protein expression or dimerization are correlated with changes in NO cofactor tetrahydrobiopterin (BH4) biosynthetic enzymes (guanosine triphosphate cyclohydrolase-1 and dihydrofolate reductase).
  
  
  
  Functional and Western blot studies were performed in streptozotocin-induced and control Sprague-Dawley female rats with DM (type 1 [t1DM]) using standardized protocols. Confirmation of xerostomia was determined by increased water intake and decreased salivary flow rate.
  
  
  
  The results showed that in female rats with DM, salivary hypofunction is correlated with decreased submandibular and parotid gland sizes. The results also show a decrease in NOS and BH4 biosynthetic enzyme in submandibular glands.
  
  
  
  These results indicate that a decrease in submandibular NO-BH4 protein expression may provide insight pertaining to mechanisms for the development of hyposalivation in DM-induced xerostomia. Furthermore, understanding the role of the NO-BH4 pathway may give insight into possible treatment options for the patient with DM experiencing xerostomia.
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, TN.
authors.forename: Cassandra R
authors.initials: CR
authors.lastname: Stewart
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, TN.
authors.forename: Nneka
authors.initials: N
authors.lastname: Obi
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, TN.
authors.forename: Elodie C
authors.initials: EC
authors.lastname: Epane
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, TN.
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Akbari
authors.affiliation: Department of Oral Surgery, School of Dentistry, Meharry Medical College.
authors.forename: Leslie
authors.initials: L
authors.lastname: Halpern
authors.affiliation: Department of Oral Surgery, School of Dentistry, Meharry Medical College.
authors.forename: Janet H
authors.initials: JH
authors.lastname: Southerland
authors.affiliation: School of Dentistry, Meharry Medical College, Nashville, TN.|Center for Women's Health Research, School of Medicine, Meharry Medical College.|Department of Physiology, School of Medicine, Meharry Medical College.
authors.forename: Pandu R
authors.initials: PR
authors.lastname: Gangula
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D048909:Diabetes Complications; D003920:Diabetes Mellitus; D005260:Female; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012471:Salivary Proteins and Peptides / Q000378:metabolism*; D014987:Xerostomia / Q000378:metabolism*
chemical_list: D012471:Salivary Proteins and Peptides; D001708:Biopterins; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin
keywords: Biopterin; diabetes mellitus; nitric oxide; nitric oxide synthase; saliva; xerostomia