Obesity associated with type 2 diabetes mellitus is linked to decreased PC1/3 mRNA expression in the Jejunum.
BACKGROUND
Bariatric surgery is the most effective therapeutic option for obesity and its complications, especially in type 2 diabetes. The aim of this study was to investigate the messenger RNA (mRNA) gene expression of proglucagon, glucose-dependent insulinotropic peptide (GIP), prohormone convertase 1/3 (PC1/3), and dipeptidyl peptidase-IV (DPP-IV) in jejunum cells of the morbidly obese (OB) non type 2 diabetes mellitus (NDM2) and type 2 diabetes mellitus (T2DM), to determine the molecular basis of incretin secretion after bariatric surgery.


METHODS
Samples of jejunal mucosa were obtained from 20 NDM2 patients: removal of a section of the jejunum about 60 cm distal to the ligament of Treitz and 18 T2DM patients: removal of a section of the jejunum about 100 cm distal to the ligament of Treitz. Total RNA was extracted using TRIzol. Reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) was carried out. Samples were sequenced to PC1/3 by ACTGene Análises Moleculares Ltd. Immuno content was quantified with a fluorescence microscope.


RESULTS
T2DM showed decreased PC1/3 mRNA expression in the primers tested (primer a, p=0.014; primer b, p=0.048). Many patients (36.5 %) did not express PC1/3 mRNA. NDM2 and T2DM subjects showed nonsignificantly different proglucagon, GIP, and DPP-IV mRNA expression. The immuno contents of glucagon-like peptide-1 and GIP decreased in T2DM jejunum, but incubation with high glucose stimulated the immuno contents.


CONCLUSIONS
The results suggest that bioactivation of pro-GIP and proglucagon could be impaired by the lower expression of PC1/3 mRNA in jejunum cells of obese patients with T2DM. However, after surgery, food could activate this system and improve glucose levels in these patients.
Departamento de Bioquímica, ICBS, UFRGS, Rua Ramiro Barcelos 2600 - anexo, CEP 90.035-003, Porto Alegre, RS, Brazil.
Francieli
F
Rohden
Cintia S
CS
Costa
Thais O
TO
Hammes
Rogério
R
Margis
Alexandre V
AV
Padoin
Cláudio C
CC
Mottin
Regina Maria
RM
Guaragna
D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007583:Jejunum / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000150:complications / Q000378:metabolism*; D045664:Proprotein Convertase 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
D012333:RNA, Messenger; C549100:pro-glucose-dependent insulinotropic polypeptide; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4; D045664:Proprotein Convertase 1