Angiotensin-Converting Enzyme Gene Polymorphism Influences Gastrointestinal Motility in Type 2 Diabetes Mellitus

Malik, Aastha; Saha, Sarama; Morya, Rajesh Kumar; Bhadada, Sanjay Kumar; Singh, Praveen; Sv, Rana

doi:10.1007/s10528-020-10011-0

Cited by 5 publications

(5 citation statements)

References 27 publications

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“…Demographic profile and biochemical parameters have been described in detail in our previous publications. 19,20 However, same salient features are presented here in Table 1. The mean age of diabetes patients was 54.6 ± 0.67 years and that of controls was 55.4 ± 0.74 years.…”

Section: Resultsmentioning

confidence: 99%

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Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus

Malik

Saha

Morya

et al. 2021

J Neurogastroenterol Motil

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Background/Aims The pathogenesis of gastrointestinal (GI) symptoms in patients with type 2 diabetes mellitus (T2DM) is yet to be delineated clearly. Serotonin, a monoamine neurotransmitter, resides primarily in the gut and plays a vital role in GI system. However, no study has been documented the role of serotonin and serotonin transporter gene (SLC6A4) polymorphism in the development of GI symptoms in T2DM patients. Methods Three hundred diabetes patients attending diabetes clinic at Postgraduate Institute of Medical Education and Research, Chandigarh, and matched healthy controls were enrolled for this study. Plasma from collected blood sample was used for serotonin measurement by enzyme-linked immunosorbent assay method and buffy coat was used for isolation of DNA by phenol chloroform method. Serotonin transporter gene polymorphism was analyzed by polymerase chain reaction method. Results The frequency of short allele (S) and SS genotype was significantly higher in patients with T2DM than controls and was associated with increased risk of T2DM. The frequency of LS genotype showed an association with protection from the disease. Regarding GI symptoms, 78.2% of patients with constipation showed LL and LS genotypes, and 97.7% of patients with diarrhea had SS genotype. The patients without GI symptoms did not show any association of gut motility with genotype. Furthermore, serotonin was significantly higher in diabetic patients who belonged to SS genotype compared to LS or LL genotype and who presented with diarrhea. Conclusion SS genotypes are prone to develop diarrhea because of faster gut motility resulting from higher serotonin levels as compared to LS and LL genotype in T2DM patients.

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Section: Resultsmentioning

confidence: 99%

“…Study design has been described in details in a previous publication. 19,20 In brief, 300 T2DM patients and 200 healthy controls were enrolled for this study. Informed consents were taken from all the study participants.…”

Section: Methodsmentioning

confidence: 99%

Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus

Malik

Saha

Morya

et al. 2021

J Neurogastroenterol Motil

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“…Demographic characteristics were described earlier in details. [14,15] In brief, out of 300 diabetic study participants, 142 were males and 96 were females. Mean age of diabetic individuals was 54.6 years (range 30-70 years).…”

Section: Resultsmentioning

confidence: 99%

“…It was conducted after receiving approval from the Institute ethics Committee, PGIME&R, Chandigarh, India. Detailed study design has been described in our previous studies [14][15][16] . In brief, 300 T2DM patients were recruited from Diabetes Clinic at PGIMER following American Diabetes Association 2013 criteria.…”

Section: Methodsmentioning

confidence: 99%

Adrenergic Receptor Beta 2and 3 Polymorphism Modulate Gastro Intestinal Motility in Ttype 2 Diabetes Mellitus Patients

Malik

Saha

et al. 2021

Preprint

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BackgroundIndividuals with type 2diabetes mellitus (T2DM) commonly present with gastro intestinal symptoms. Exact pathophysiology behind these symptoms is not elucidated. Previous studies reported the role of adrenoceptors on gut motility. However, no study has been conducted to observe whether adrenergic beta receptor (ADRB) 2 and 3 gene polymorphism could influence the gut motility in T2DM. Materials and Methods:Three hundred T2DM patients and 200 age and sex matched healthy controls were enrolled for this study. Participants were subjected to lactulose hydrogen breath test for estimation of orocecal transit time (OCTT). To carry out polymorphism study, buffy coat of EDTA blood was used for DNA isolation followed by polymerase chain reaction and restriction fragment length polymorphism. Results:In this study, the frequency of C allele as well as CC genotype of ADRB3 gene polymorphism and A allele as well as AA genotype of ADRB2 gene polymorphism were significantly higher in patients than controls and was associated with increased risk for T2DM. On comparison of gut motility, OCTT was found to be significantly prolonged (p<0.01) in individuals with CC genotype compared to TT or CT genotype in ADRB3 polymorphism and AA genotype, compared to AG and GG genotype in case of ADRB2 polymorphism. Combined effect of both adrenoceptors on gut motility revealed that individuals having AG or AA genotype in combination with other genotypes had significantly prolonged OCTT. Conclusion:It could be concluded that beta adrenoceptor gene polymorphism has significant role on regulation of gut motility in T2DM.

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“…Curiously, the human colonic smooth muscle is more sensitive to Ang II than to acetylcholine (ACh), but the physiological importance of Ang II in the GI tract is still not completely understood [ 25 , 30 , 31 ]. Interestingly, there is little information on RAS alterations in the intestine of diabetic individuals, but recently one study concluded that ACE gene polymorphism in patients with T2DM influences intestinal motility, since those patients presented a prevalent genotype that was associated to constipation [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats

Esteves-Monteiro

Menezes-Pinto

Ferreira‐Duarte

et al. 2022

IJMS

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Diabetes mellitus (DM) is a chronic progressive metabolic disorder associated with several gastrointestinal complications, affecting up to 75% of patients. Knowing that Angiotensin II (AngII) also regulates intestinal contraction, we decided to evaluate changes in ileum and colon histomorphometry and AngII reactivity in a rat model of DM. Streptozotocin (STZ, 55 mg/kg) was administered to induce DM to 24 adult male Wistar rats. Diabetic rats displayed all the characteristic signs of type 1 DM (T1DM) and fecal excretion increased about 4-fold over 14 days, while the excretion of controls remained unaltered. Compared to controls, diabetic ileum and colon presented an increase in both macroscopic (length, perimeter and weight) and microscopic (muscular wall thickness) parameters. Functionally, AngII-induced smooth muscle contraction was lower in diabetic rats, except in the distal colon. These differences in the contractile response to AngII may result from an imbalance between AngII type 1 (antagonized by candesartan, 10 nM) and type 2 receptors activation (antagonized by PD123319, 100 nM). Taken together, these results indicate that an early and refined STZ-induced T1DM rat model already shows structural remodelling of the gut wall and decreased contractile response to AngII, findings that may help to explain diabetic dysmotility.

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Angiotensin-Converting Enzyme Gene Polymorphism Influences Gastrointestinal Motility in Type 2 Diabetes Mellitus

Cited by 5 publications

References 27 publications

Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus

Impact of serotonin transporter gene polymorphism on gut motility in patients with type 2 Diabetes mellitus

Adrenergic Receptor Beta 2and 3 Polymorphism Modulate Gastro Intestinal Motility in Ttype 2 Diabetes Mellitus Patients

Histomorphometry Changes and Decreased Reactivity to Angiotensin II in the Ileum and Colon of Streptozotocin-Induced Diabetic Rats

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