Global Advanced Research Journal of Medicine and Medical Sciences (GARJMMS) ISSN: 2315-5159
October 2015 Vol. 4(10), pp. 441-448
Copyright © 2015 Global Advanced Research Journals


Full Length Research Paper

Brain Serotonergic Disturbances Caused by Diabetes Mellitus are not Reversed by Insulin Treatment

Gabriel Manjarrez-Gutiérrez1,2*, Teresa Neri-Gómez1, Rocío Herrera-Márquez1, José Antonio Mondragón-Herrera1, Alfonso Boyzo-Montes de Oca3 and Jorge Hernandez-Rodríguez3

1Laboratory of Molecular Pathology, Cardiology Hospital, National Medical Center (CMN-SXXI), Mexican Institute of Social Security (IMSS), Mexico City, Mexico
2Medical Research Unit in Neurological Diseases, Specialties Hospital, CMN-SXXI, IMSS, México, DF, México
3Laboratory of Neurontogeny, Department of Physiology, Biophysics and Neurosciences, Center of Research and Advanced Studies (CINVESTAV) IPN, Mexico City, Mexico.

*Corresponding Author E-mail:,; Phone: (+52) (55) 56276900, Ext. 22156; Fax: (+52) (55) 55780240;

Accepted 05 October 2015 


The aim of this study was to determine whether changes in the kinetics and the capacity of phosphorylation of the tryptophan-5-hydroxylase (TPH) in diabetic rats are normalized with insulin, or if there are changes in expressions of TPH1 or TPH2 as mechanisms that explain the chronic inhibition of the biosynthesis of brain 5-hydroxytryptamine (5-HT). A diabetic mellitus (DM) model was produced through the administration of streptozotocin and controls (STZ).  After 7 days,the diabetic rats were divided into two subgroups. One group was treated with insulin and the other did not receive treatment. After 7, 14 and 21 days, the brainstem was removed to determine: L-tryptophan (L-Trp), 5-HT, TPH activity, by observing the kinetics and activation through phosphorylating conditions. Besides, the expressions of TPH1, TPH2 and TPH-phosphorylated–S19 (TPH2-PS-19) were assessed by Western blot. The diabetic rats had a decrease of L-Trp, 5-HT and TPH activity; a decrease of the Vmax and an increase in Km. They also showed less activation of the TPH by phosphorylation and a reduced expression of TPH1, TPH2 and TPH2-PS-19. Interestingly enough, all these changes are not normalized in the diabetic rats subgroup treated with insulin. A decrease in the synthesis of brain serotonin during the diabetic state was confirmed, due to changes in the kinetics and phosphorylation capacity of TPH and a decreased expression of TPH1, TPH2 and TPH2-PS-19, which did not return to normal levels with insulin. These findings support the fact that chronic inhibition of  5-HT biosynthesis resistant to insulin is due to the decrease of TPH’s expression and activity as a consequence of metabolic changes during the diabetic state.

Keywords: Brain, Diabetes mellitus, Insulin, Serotonin, Tryptophan-5-hydroxylase

Related Articles

Original Research Article
Irshad M, Asif Iqbal, Ansari MA and Raghavendra L
Relation of insulin resistance (IR) with viral etiology and blood level of cytokines in patients with liver diseases
Glo. Adv. Res. J. Med. Med. Sci. March 2013 Vol: 2(3): - [Abstract] [Full Text - PDF] (280 KB)
Case Report
Lopez Goerne T, Arevalo A, Ramirez P and Larraza P
Copper nanoparticles as treatment of diabetic foot ulcers: A case report
Glo. Adv. Res. J. Med. Med. Sci. October 2017 Vol: 6(10): - [Abstract] [Full Text - PDF] (960 KB)
Original Research Articles
Gede Wira Mahadita, Made Jawi and Ketut Suastika
Purple sweet potato tuber extract lowers mallondialdehyde and improves glycemic control in subjects with type 2 diabetes mellitus
Glo. Adv. Res. J. Med. Med. Sci. July 2016 Vol: 5(7): - [Abstract] [Full Text - PDF] (224 KB)
Saleh A S AL-Abdulhadi
Spotlight into some Abnormalities of Human Chromosome in Saudi Arabia
Glo. Adv. Res. J. Med. Med. Sci. January 2018 Vol: 7(1): - [Abstract] [Full Text - PDF] (257 KB)
Millán-Guerrero RO, García-Ramírez AL, Trujillo-Hernández B, Caballero-Hoyos R, González–Pérez O, Isais-Millan S and Trujillo-Magallon Erick
Efficacy of α-lipoic acid in the treatment of diabetic polyneuropathy. A Randomized, Double-Blind Study
Glo. Adv. Res. J. Med. Med. Sci. December 2018 Vol: 7(10): - [Abstract] [Full Text - PDF] (172 KB)
Maimoona Mushtaq Ahmed
Clinical presentation of diabetic emergencies in university hospital
Glo. Adv. Res. J. Med. Med. Sci. October 2014 Vol: 3(10): - [Abstract] [Full Text - PDF] (380 KB)

Current Issue

Viewing Options

View Full Article - PDF
Download Full Article - PDF

Search for Articles

Gabriel Manjarrez-Gutiérrez on Google Scholar
Gabriel Manjarrez-Gutiérrez on Pubmed
Teresa Neri-Gómez on Google Scholar
Teresa Neri-Gómez on Pubmed
Rocío Herrera-Márquez on Google Scholar
Rocío Herrera-Márquez on Pubmed
José Antonio Mondragón-Herrera on Google Scholar
José Antonio Mondragón-Herrera on Pubmed
Alfonso Boyzo-Montes de Oca on Google Scholar
Alfonso Boyzo-Montes de Oca on Pubmed
Jorge Hern on Google Scholar
Jorge Hern on Pubmed
ez-Rodríguez on Google Scholar
ez-Rodríguez on Pubmed


Viewed 3511
Printed 669
Downloaded 1546
Powered By iPortal Works