Gastrointestinal Complications of Diabetes Mellitus

Montgomery, Patricia A.

doi:10.1300/j088v07n02_03

Cited by 3 publications

(3 citation statements)

References 101 publications

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“…The most common etiologies of Gp include idiopathic, post-surgical/iatrogenic, and a severe complication of uncontrolled diabetes mellitus (DM) [ 4 ]. Numerous lines of evidence suggest the loss of enteric neuronal nitric oxide synthase (nNOS) and nitric oxide (NO)-mediated relaxation of gastric smooth muscle as the primary culprits of Gp in diabetic patients [ 5 , 6 , 7 , 8 ]. In addition, oxidative stress associated with hyperglycemia and obesity are known contributors to the pathogenesis of diabetic Gp [ 9 , 10 ].…”

Section: Introductionmentioning

confidence: 99%

Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice

2020

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Gastroparesis (Gp) is a multifactorial condition commonly observed in females and is characterized by delayed or rapid gastric emptying (GE). The role of ovarian hormones on GE in the pathogenesis of obesity induced type 2 diabetes mellitus (T2DM) is completely unknown. The aims of our study are to investigate whether supplementation of 17β-estradiol (E2) or progesterone (P4) restores impaired nuclear factor erythroid 2-related factor 2 (Nrf2, an oxidative stress-responsive transcription factor) and nitric oxide (NO)-mediated gastric motility in ovariectomized (OVX) mice consuming a high-fat diet (HFD, a model of T2DM). Groups of OVX+HFD mice were administered daily subcutaneous doses of either E2 or P4 for 12 weeks. The effects of E2 and P4 on body weight, metabolic homeostasis, solid GE, gastric antrum NO-mediated relaxation, total nitrite levels, neuronal nitric oxide synthase (nNOSα), and its cofactor expression levels were assessed in OVX+HFD mice. HFD exacerbated hyperglycemia and insulinemia while accelerating GE (p < 0.05) in OVX mice. Exogenous E2, but not P4, attenuated rapid gastric emptying and restored gastric nitrergic relaxation, total nitrite levels, nNOSα, and cofactor expression via normalizing Nrf2-Phase II enzymes, inflammatory response, and mitogen-activated protein kinase (MAPK) protein expression in OVX+HFD mice. We conclude that E2 is beneficial in normalizing metabolic homeostasis and gastric emptying in obese, diabetic OVX mice consuming a fat-rich diet.

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Section: Introductionmentioning

confidence: 99%

Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice

2020

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“…Gastrointestinal (GI) dysfunction occurs in as many as 20-50% of patients with diabetes mellitus (T1/T2DM) [1]. Diabetic gastroparesis is a syndrome of delayed gastric emptying (GE) in the absence of mechanical obstruction of the upper stomach, antrum body, lower pyloric sphincter, and duodenum.…”

Section: Introductionmentioning

confidence: 99%

Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model

2020

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Background Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods Gastric neuromuscular sections from adult female C57BL/6 J mice were incubated in normoglycemic (NG, 5 mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 h. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p < 0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia.

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“…current treatment models include dietary modifications, oral drug therapy (antibiotics, dopamine-2 (D2) receptor antagonists), and surgery [1,9]. However, despite extensive research, drug therapy that can improve gastric emptying and decrease symptoms, without too many side effects are limited.…”

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confidence: 99%

Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

Sprouse

Sampath

Gangula

2019

Preprint

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Background: Gastroparesis, a condition of abnormal gastric emptying, is most commonly observed in diabetic women. To date, the role of ovarian hormones and/or gastric hormone receptors on regulating nitrergic-mediated gastric motility remains inconclusive. Aim: The purpose of this study is to investigate whether sex hormones/their receptors can attenuate altered Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), neuronal Nitric Oxide Synthase (nNOS) expression and nitrergic relaxation in gastric neuromuscular tissues exposed to in-vitro hyperglycemia (HG). Methods: Gastric neuromuscular sections from adult female C57BL/6J mice were incubated in normoglycemic (NG, 5mM) or hyperglycemic (30 mM or 50 mM) conditions in the presence or absence of selective estrogen receptor (ER) agonists (ERα /PPT or ERβ: DPN); or non-selective sex hormone receptor antagonists (ER/ICI 182,780, or progesterone receptor (PR)/ RU486) for 48 hours. mRNA, protein expression and nitrergic relaxation of circular gastric neuromuscular strips were assessed. Results: Our findings in HG, compared to NG, demonstrate a significant reduction in ER, Nrf2, and nNOS expression in gastric specimens. In addition, in-vitro treatment with sex hormones and/or their agonists significantly (*p<0.05) restored Nrf2/nNOSα expression and total nitrite production. Conversely, ER, but not PR, antagonist significantly reduced Nrf2/nNOSα expression and nitrergic relaxation. Conclusions: Our data suggest that ER’s can regulate nitrergic function by improving Nrf2/nNOS expression in experimental hyperglycemia. Keywords: Gastroparesis; Sex Hormones; Estrogen Receptors; Drug Therapy; nNOS, Nrf2, Nitrergic Relaxation

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Gastrointestinal Complications of Diabetes Mellitus

Cited by 3 publications

References 101 publications

Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice

Supplementation of 17β-Estradiol Normalizes Rapid Gastric Emptying by Restoring Impaired Nrf2 and nNOS Function in Obesity-Induced Diabetic Ovariectomized Mice

Role of sex hormones and their receptors on gastric Nrf2 and neuronal nitric oxide synthase function in an experimental hyperglycemia model

Role of Sex Hormones And Their Receptors On Gastric Nrf2 And Neuronal Nitric Oxide Synthase Function In An Experimental Hyperglycemia Model

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