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.
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 obesepatients with T2DM. However, after surgery, food could activate this system and improve glucose levels in these patients.
Authors: N B Jørgensen; S H Jacobsen; C Dirksen; K N Bojsen-Møller; L Naver; L Hvolris; T R Clausen; B S Wulff; D Worm; D Lindqvist Hansen; S Madsbad; J J Holst Journal: Am J Physiol Endocrinol Metab Date: 2012-04-24 Impact factor: 4.310